PHIPpleckstrin homology domain interacting protein

SFARI Gene Score

High Confidence, Syndromic Criteria 1.1, Syndromic

Autism Reports / Total Reports

8 / 28

Rare Variants / Common Variants

136 / 0

Aliases

PHIP, BRWD2, DCAF14, WDR11, ndrp

Associated Syndromes

Chung-Jansen syndrome, DD, Chung-Jansen syndrome, DD, ID, Chung-Jansen syndrome

Chromosome Band

6q14.1

Associated Disorders

DD/NDD, ADHD, ASD, EPS

Relevance to Autism

Molecular Function

Probable regulator of the insulin and insulin-like growth factor signaling pathways. Stimulates cell proliferation through regulation of cyclin transcription and has an anti-apoptotic activity through AKT1 phosphorylation and activation. Plays a role in the regulation of cell morphology and cytoskeletal organization.

External Links

Gene Card Open Targets Platform gnomAD browser PubMed

Human

Entrez Gene OMIM UniProt HumanBase VariCarta

SFARI Genomic Platforms

GPF browser SFARI genome browser

Reports (28)
Variants (136)
Gene Score

Reports related to PHIP (28 Reports)

#	Type	Title	Author, Year	Autism Report	Associated Disorders
1	Primary	The contribution of de novo coding mutations to autism spectrum disorder	Iossifov I et al. (2014)	Yes	-
2	Support	De novo genic mutations among a Chinese autism spectrum disorder cohort	Wang T , et al. (2016)	Yes	-
3	Support	The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies	Redin C , et al. (2016)	No	PDD, epilepsy/seizures
4	Recent Recommendation	De novo PHIP-predicted deleterious variants are associated with developmental delay, intellectual disability, obesity, and dysmorphic features	Webster E , et al. (2016)	No	Anxiety, hypotonia, obesity
5	Support	Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases	Stessman HA , et al. (2017)	No	-
6	Support	A clinical utility study of exome sequencing versus conventional genetic testing in pediatric neurology	Vissers LE , et al. (2017)	No	-
7	Support	Using medical exome sequencing to identify the causes of neurodevelopmental disorders: Experience of 2 clinical units and 216 patients	Chrot E , et al. (2017)	No	-
8	Support	Expanding the genetic heterogeneity of intellectual disability	Anazi S , et al. (2017)	No	-
9	Support	Genomic Patterns of De Novo Mutation in Simplex Autism	Turner TN et al. (2017)	Yes	-
10	Recent Recommendation	A genotype-first approach identifies an intellectual disability-overweight syndrome caused by PHIP haploinsufficiency	Jansen S , et al. (2017)	No	ASD or autistic features
11	Support	Clinical and genetic characterization of individuals with predicted deleterious PHIP variants	Craddock KE , et al. (2019)	No	ASD or autistic features, ADHD
12	Recent Recommendation	Exome Sequencing Identifies Genes and Gene Sets Contributing to Severe Childhood Obesity, Linking PHIP Variants to Repressed POMC Transcription	Marenne G et al. (2020)	No	Autistic features, behavioral abnormalities
13	Support	Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders	Wang T et al. (2020)	Yes	-
14	Support	-	Rodin RE et al. (2021)	Yes	-
15	Support	-	Kritioti E et al. (2021)	No	-
16	Support	-	ÃÂlvarez-Mora MI et al. (2022)	No	-
17	Support	-	Woodbury-Smith M et al. (2022)	Yes	-
18	Support	-	Brea-FernÃÂ¡ndez AJ et al. (2022)	No	-
19	Support	-	Hu C et al. (2022)	Yes	-
20	Support	-	Tirado-Class N et al. (2022)	No	ASD
21	Support	-	Zhou X et al. (2022)	Yes	-
22	Recent Recommendation	-	Kampmeier A et al. (2023)	No	ASD, ADHD, epilepsy/seizures
23	Support	-	Spataro N et al. (2023)	No	ADHD, dyslexia
24	Support	-	Thomas V Fernandez et al. (2023)	No	-
25	Support	-	Khemika K Sudnawa et al. (2024)	No	ASD
26	Support	-	Axel Schmidt et al. (2024)	No	ID, cognitive impairment
27	Support	-	Mathew Wallis et al. (2024)	No	-
28	Support	-	Jonathan de Fallois et al. (2024)	No	-

Rare Variants (136)

Allele Change	Residue Change	Variant Type	Inheritance Pattern	Parental Transmission	Family Type	PubMed ID	Author, Year
-	-	translocation	-	-	-	29209020	Jansen S , et al. (2017)
-	-	copy_number_loss	-	-	-	29209020	Jansen S , et al. (2017)
-	-	copy_number_loss	De novo	-	-	27841880	Redin C , et al. (2016)
-	-	copy_number_loss	De novo	-	-	36726590	Kampmeier A et al. (2023)
-	-	copy_number_loss	Unknown	-	-	36726590	Kampmeier A et al. (2023)
-	p.Arg250Ter	stop_gained	De novo	-	-	32492392	Marenne G et al. (2020)
-	p.Arg721Ter	stop_gained	Unknown	-	-	32492392	Marenne G et al. (2020)
-	p.Gln1343Ter	stop_gained	Unknown	-	-	32492392	Marenne G et al. (2020)
c.748C>T	p.Arg250Ter	stop_gained	De novo	-	-	35982159	Zhou X et al. (2022)
c.1880-2dup	-	splice_site_variant	Unknown	-	-	33004838	Wang T et al. (2020)
-	-	copy_number_loss	Familial	Maternal	-	36726590	Kampmeier A et al. (2023)
-	-	copy_number_loss	Familial	Paternal	-	36726590	Kampmeier A et al. (2023)
c.1186C>T	p.Arg396Ter	stop_gained	Unknown	-	-	33004838	Wang T et al. (2020)
c.1663C>T	p.Gln555Ter	stop_gained	Unknown	-	-	33004838	Wang T et al. (2020)
c.2854C>T	p.Arg952Ter	stop_gained	Unknown	-	-	33004838	Wang T et al. (2020)
c.1186C>T	p.Arg396Ter	stop_gained	De novo	-	-	35982159	Zhou X et al. (2022)
-	-	complex_structural_alteration	De novo	-	-	27841880	Redin C , et al. (2016)
-	p.Arg1718Ser	missense_variant	Unknown	-	-	32492392	Marenne G et al. (2020)
c.3193C>T	p.Arg1065Ter	stop_gained	Unknown	-	-	33004838	Wang T et al. (2020)
c.4276A>T	p.Lys1426Ter	stop_gained	Unknown	-	-	33004838	Wang T et al. (2020)
c.5227C>T	p.Arg1743Ter	stop_gained	Unknown	-	-	33004838	Wang T et al. (2020)
c.3536-7A>G	-	splice_region_variant	De novo	-	-	35982159	Zhou X et al. (2022)
c.823-2A>G	-	splice_site_variant	Unknown	-	-	32492392	Marenne G et al. (2020)
c.820C>T	p.Gln274Ter	stop_gained	De novo	-	-	29209020	Jansen S , et al. (2017)
c.894G>A	p.Trp298Ter	stop_gained	Unknown	-	-	36980980	Spataro N et al. (2023)
c.1524+1G>T	-	splice_site_variant	Unknown	-	-	32492392	Marenne G et al. (2020)
-	-	copy_number_loss	Unknown	Not maternal	-	36726590	Kampmeier A et al. (2023)
c.235T>C	p.Cys79Arg	missense_variant	De novo	-	-	33004838	Wang T et al. (2020)
c.3892C>T	p.Arg1298Ter	stop_gained	De novo	-	-	28708303	Chrot E , et al. (2017)
c.20G>A	p.Gly7Asp	missense_variant	De novo	-	-	33432195	Rodin RE et al. (2021)
c.2902C>T	p.Arg968Ter	stop_gained	De novo	-	-	29209020	Jansen S , et al. (2017)
c.3433A>G	p.Arg1145Gly	missense_variant	Unknown	-	-	35741772	Hu C et al. (2022)
c.589C>T	p.Arg197Trp	missense_variant	Unknown	-	-	33004838	Wang T et al. (2020)
c.694G>A	p.Ala232Thr	missense_variant	Unknown	-	-	33004838	Wang T et al. (2020)
c.749G>A	p.Arg250Gln	missense_variant	Unknown	-	-	33004838	Wang T et al. (2020)
c.868G>A	p.Gly290Arg	missense_variant	Unknown	-	-	33004838	Wang T et al. (2020)
c.949C>T	p.Arg317Cys	missense_variant	Unknown	-	-	33004838	Wang T et al. (2020)
c.3447T>G	p.Tyr1149Ter	stop_gained	De novo	-	-	29209020	Jansen S , et al. (2017)
c.3571C>T	p.Gln1191Ter	stop_gained	De novo	-	-	29209020	Jansen S , et al. (2017)
c.3892C>T	p.Arg1298Ter	stop_gained	De novo	-	-	29209020	Jansen S , et al. (2017)
c.4060A>T	p.Arg1354Ter	stop_gained	Unknown	-	-	29209020	Jansen S , et al. (2017)
c.1013C>T	p.Thr338Met	missense_variant	Unknown	-	-	33004838	Wang T et al. (2020)
c.1471G>A	p.Val491Met	missense_variant	Unknown	-	-	33004838	Wang T et al. (2020)
c.2071C>T	p.Arg691Cys	missense_variant	Unknown	-	-	33004838	Wang T et al. (2020)
c.2903G>A	p.Arg968Gln	missense_variant	Unknown	-	-	33004838	Wang T et al. (2020)
c.2903G>C	p.Arg968Pro	missense_variant	Unknown	-	-	33004838	Wang T et al. (2020)
c.2935C>T	p.Arg979Trp	missense_variant	Unknown	-	-	33004838	Wang T et al. (2020)
c.3139G>A	p.Asp1047Asn	missense_variant	Unknown	-	-	33004838	Wang T et al. (2020)
c.3611C>T	p.Thr1204Met	missense_variant	Unknown	-	-	33004838	Wang T et al. (2020)
c.3764T>A	p.Leu1255His	missense_variant	Unknown	-	-	33004838	Wang T et al. (2020)
c.3928C>T	p.Arg1310Cys	missense_variant	Unknown	-	-	33004838	Wang T et al. (2020)
c.3929G>A	p.Arg1310His	missense_variant	Unknown	-	-	33004838	Wang T et al. (2020)
c.4759C>T	p.Arg1587Cys	missense_variant	Unknown	-	-	33004838	Wang T et al. (2020)
c.4760G>A	p.Arg1587His	missense_variant	Unknown	-	-	33004838	Wang T et al. (2020)
c.50T>C	p.Phe17Ser	missense_variant	De novo	-	-	27900362	Webster E , et al. (2016)
c.3706C>T	p.Arg1236Ter	stop_gained	Unknown	-	-	36726590	Kampmeier A et al. (2023)
c.1362C>A	p.Tyr454Ter	stop_gained	De novo	-	-	28191889	Stessman HA , et al. (2017)
c.328C>A	p.Arg110Ser	missense_variant	De novo	-	-	29209020	Jansen S , et al. (2017)
c.328C>T	p.Arg110Cys	missense_variant	De novo	-	-	29209020	Jansen S , et al. (2017)
c.865A>C	p.Thr289Pro	missense_variant	Unknown	-	-	32492392	Marenne G et al. (2020)
c.3536-4_3540del	-	splice_site_variant	De novo	-	-	32492392	Marenne G et al. (2020)
c.3161del	p.Leu1054Ter	stop_gained	De novo	-	-	31167805	Craddock KE , et al. (2019)
c.3595del	p.Val1199Ter	stop_gained	De novo	-	-	31167805	Craddock KE , et al. (2019)
c.577C>T	p.Arg193Ter	stop_gained	De novo	-	Simplex	28940097	Anazi S , et al. (2017)
c.91G>T	p.Ala31Ser	missense_variant	De novo	-	Simplex	35982159	Zhou X et al. (2022)
c.92C>T	p.Ala31Val	missense_variant	De novo	-	Simplex	35982159	Zhou X et al. (2022)
-	p.Thr1506Ala	missense_variant	Familial	Paternal	-	32492392	Marenne G et al. (2020)
c.3787C>G	p.Gln1263Glu	missense_variant	De novo	-	-	29209020	Jansen S , et al. (2017)
c.4241T>C	p.Phe1414Ser	missense_variant	De novo	-	-	32492392	Marenne G et al. (2020)
-	p.Lys1443ThrfsTer11	frameshift_variant	Unknown	-	-	32492392	Marenne G et al. (2020)
c.439+1G>T	-	splice_site_variant	De novo	-	Simplex	36726590	Kampmeier A et al. (2023)
c.686C>T	p.Ser229Leu	missense_variant	De novo	-	-	31167805	Craddock KE , et al. (2019)
c.860C>A	p.Ser287Tyr	missense_variant	De novo	-	-	31167805	Craddock KE , et al. (2019)
c.328C>T	p.Arg110Cys	missense_variant	De novo	-	Simplex	35982159	Zhou X et al. (2022)
c.921_923+2del	-	frameshift_variant	De novo	-	Simplex	28965761	Turner TN et al. (2017)
c.1562A>G	p.Lys521Arg	missense_variant	De novo	-	-	31167805	Craddock KE , et al. (2019)
c.1046T>A	p.Phe349Tyr	missense_variant	Familial	Paternal	-	35741772	Hu C et al. (2022)
c.1507C>T	p.Arg503Ter	stop_gained	De novo	-	Simplex	36726590	Kampmeier A et al. (2023)
c.4370G>A	p.Ser1457Asn	missense_variant	Unknown	-	-	39039281	Axel Schmidt et al. (2024)
c.3790A>G	p.Thr1264Ala	missense_variant	Familial	Paternal	-	35741772	Hu C et al. (2022)
c.779del	p.Leu260TrpfsTer48	frameshift_variant	De novo	-	-	33004838	Wang T et al. (2020)
c.3947dup	p.Tyr1316Ter	frameshift_variant	Unknown	-	-	36726590	Kampmeier A et al. (2023)
c.1463A>T	p.Asp488Val	missense_variant	De novo	-	-	35863899	Tirado-Class N et al. (2022)
c.2888A>G	p.Glu963Gly	missense_variant	De novo	-	-	35863899	Tirado-Class N et al. (2022)
c.2304del	p.Thr770LeufsTer43	frameshift_variant	Unknown	-	-	33004838	Wang T et al. (2020)
c.1050dup	p.Gly351TrpfsTer16	frameshift_variant	De novo	-	-	35982159	Zhou X et al. (2022)
c.2925C>T	p.Val975%3D	synonymous_variant	De novo	-	Simplex	35982159	Zhou X et al. (2022)
c.2995C>A	p.Arg999%3D	synonymous_variant	De novo	-	Simplex	35982159	Zhou X et al. (2022)
c.1653+1G>A	-	splice_site_variant	Unknown	Not maternal	-	29209020	Jansen S , et al. (2017)
c.3440del	p.Leu1147GlnfsTer26	frameshift_variant	De novo	-	-	35982159	Zhou X et al. (2022)
c.1900C>T	p.Gln634Ter	stop_gained	Unknown	Not maternal	-	29209020	Jansen S , et al. (2017)
c.774dup	p.Pro259ThrfsTer9	frameshift_variant	Unknown	-	-	29209020	Jansen S , et al. (2017)
c.1139_1142del	p.Phe380Ter	frameshift_variant	De novo	-	-	36980980	Spataro N et al. (2023)
c.3274C>T	p.Gln1092Ter	stop_gained	Familial	Paternal	-	36726590	Kampmeier A et al. (2023)
c.4513C>T	p.Arg1505Ter	stop_gained	Familial	Paternal	-	36726590	Kampmeier A et al. (2023)
c.76G>A	p.Gly26Arg	missense_variant	De novo	-	-	39156152	Jonathan de Fallois et al. (2024)
c.860C>A	p.Ser287Tyr	missense_variant	De novo	-	Simplex	36726590	Kampmeier A et al. (2023)
c.3311A>T	p.Asn1104Ile	missense_variant	Unknown	-	-	35205252	Woodbury-Smith M et al. (2022)
c.1165G>A	p.Ala389Thr	missense_variant	Familial	Paternal	-	32492392	Marenne G et al. (2020)
c.1225C>T	p.Arg409Cys	missense_variant	Familial	Paternal	-	32492392	Marenne G et al. (2020)
c.779del	p.Leu260TrpfsTer48	frameshift_variant	De novo	-	-	27900362	Webster E , et al. (2016)
c.3787C>G	p.Gln1263Glu	missense_variant	De novo	-	Simplex	25363768	Iossifov I et al. (2014)
c.1043A>C	p.Tyr348Ser	missense_variant	De novo	-	Simplex	36726590	Kampmeier A et al. (2023)
c.1525A>T	p.Ile509Phe	missense_variant	De novo	-	Simplex	36726590	Kampmeier A et al. (2023)
c.2888A>G	p.Glu963Gly	missense_variant	De novo	-	Simplex	36726590	Kampmeier A et al. (2023)
c.4516A>G	p.Thr1506Ala	missense_variant	Familial	Paternal	-	32492392	Marenne G et al. (2020)
c.241C>T	p.Arg81Ter	stop_gained	De novo	-	Simplex	39156152	Jonathan de Fallois et al. (2024)
c.5300_5301del	p.Arg1767AsnfsTer2	frameshift_variant	De novo	-	-	27824329	Wang T , et al. (2016)
c.298_299del	p.Leu100IlefsTer13	frameshift_variant	De novo	-	-	29209020	Jansen S , et al. (2017)
c.919_923del	p.Ile307ProfsTer22	frameshift_variant	De novo	-	-	29209020	Jansen S , et al. (2017)
c.829C>A	p.Pro277Thr	missense_variant	Familial	Maternal	-	39095811	Mathew Wallis et al. (2024)
c.5317C>T	p.Arg1773Ter	stop_gained	De novo	-	Simplex	35183220	ÃÂlvarez-Mora MI et al. (2022)
c.5072C>T	p.Thr1691Ile	missense_variant	De novo	-	-	35322241	Brea-FernÃÂ¡ndez AJ et al. (2022)
c.1663C>T	p.Gln555Ter	stop_gained	Familial	Paternal	Multiplex	29209020	Jansen S , et al. (2017)
c.4570del	p.Ser1524LeufsTer22	frameshift_variant	Unknown	-	-	31167805	Craddock KE , et al. (2019)
c.3502dup	p.Ile1168AsnfsTer43	frameshift_variant	Unknown	-	-	39039281	Axel Schmidt et al. (2024)
c.50T>G	p.Phe17Cys	missense_variant	De novo	-	Simplex	37788244	Thomas V Fernandez et al. (2023)
c.3801_3805del	p.Ile1268SerfsTer4	frameshift_variant	De novo	-	-	29209020	Jansen S , et al. (2017)
c.340+2T>C	-	splice_site_variant	Unknown	Not maternal	Multiplex	29209020	Jansen S , et al. (2017)
c.919_923del	p.Ile307ProfsTer22	frameshift_variant	De novo	-	-	28333917	Vissers LE , et al. (2017)
c.4415_4418del	p.Glu1472AlafsTer22	frameshift_variant	De novo	-	-	29209020	Jansen S , et al. (2017)
c.919_923del	p.Ile307ProfsTer22	frameshift_variant	De novo	-	-	39039281	Axel Schmidt et al. (2024)
c.2231_2232insGAG	p.Gly744_Glu745insArg	inframe_insertion	De novo	-	-	35982159	Zhou X et al. (2022)
c.3631_3634del	p.Gln1211AspfsTer13	frameshift_variant	De novo	-	-	34324503	Kritioti E et al. (2021)
c.3782+3_3782+6del	-	splice_site_variant	Unknown	Not maternal	-	31167805	Craddock KE , et al. (2019)
c.3947dup	p.Tyr1316Ter	frameshift_variant	Unknown	Not maternal	-	36726590	Kampmeier A et al. (2023)
c.2744_2747del	p.Lys915SerfsTer15	frameshift_variant	De novo	-	-	31167805	Craddock KE , et al. (2019)
c.180_182del	p.Tyr60_Gln61delinsTer	frameshift_variant	Unknown	-	-	36726590	Kampmeier A et al. (2023)
c.2048C>A	p.Ser683Ter	stop_gained	Unknown	Not maternal	Multiplex	36726590	Kampmeier A et al. (2023)
c.1050del	p.Phe350LeufsTer32	frameshift_variant	Unknown	Not maternal	-	29209020	Jansen S , et al. (2017)
c.2306_2309del	p.Pro769LeufsTer43	frameshift_variant	De novo	-	Simplex	36726590	Kampmeier A et al. (2023)
c.3631_3634del	p.Gln1211AspfsTer13	frameshift_variant	De novo	-	Simplex	36726590	Kampmeier A et al. (2023)
c.637_638del	p.Asp213Ter	stop_gained	Familial	Maternal	Multiplex	39156152	Jonathan de Fallois et al. (2024)
c.598_599delinsT	p.Thr200LeufsTer8	frameshift_variant	Unknown	Not paternal	-	31167805	Craddock KE , et al. (2019)
c.540_541insA	p.Gly181ArgfsTer12	frameshift_variant	Familial	Paternal	Unknown	31167805	Craddock KE , et al. (2019)
c.2521_2522insCACACACA	p.Ser841ThrfsTer65	frameshift_variant	Familial	Maternal	-	36726590	Kampmeier A et al. (2023)

Common Variants

No common variants reported.

Current Score
Scoring History
3rd Party Scoring

SFARI Gene score

High Confidence, Syndromic

Score Delta: Score remained at 1S

criteria met

See SFARI Gene'scoring criteria

High Confidence

See all Category 1 Genes

We considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.

Syndromic

See all Category S Genes

The syndromic category includes mutations that are associated with a substantial degree of increased risk and consistently linked to additional characteristics not required for an ASD diagnosis. If there is independent evidence implicating a gene in idiopathic ASD, it will be listed as "#S" (e.g., 2S, 3S, etc.). If there is no such independent evidence, the gene will be listed simply as "S."

1/1/2021

Score remained at 1

Description

A de novo potentially damaging missense variant in the PHIP gene was identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014); a de novo frameshift variant in this gene was identified in an ASD proband from the Autism Clinical and Genetic Resources in China (ACGC) cohort (Wang et al., 2016). A second de novo loss-of-function (LoF) variant in PHIP was identified in an ASD proband from the Simons Simplex Collection in Turner et al., 2017. De novo variants in this gene have also been identified in patients presenting with developmental delay/intellectual disability in multiple reports (Webster et al., 2016; Redin et al., 2017; Stessman et al. ,2017; Vissers et al., 2017; Cherot et al., 2017). A clinical evaluation of 23 individuals with PHIP variants in Jansen et al., 2017 identified a syndromic form of developmental delay/intellectual disability in which most individuals (17/23, 74%) were overweight or obese; behavioral problems, including autistic features, were observed in 18 out of 23 individuals (78%). Craddock et al., 2019 described 10 novel individuals with PHIP-related DIDOD syndrome; all ten individuals presented with developmental delay/intellectual disability, and ASD or autistic features were observed in 6/9 individuals.

Reports Added

[The landscape of somatic mutation in cerebral cortex of autistic and neurotypical individuals revealed by ultra-deep whole-genome sequencing2021]

10/1/2020

Score remained at 1

Description

Reports Added

[Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders2020]

7/1/2020

Score remained at 1

Description

Reports Added

[Exome Sequencing Identifies Genes and Gene Sets Contributing to Severe Childhood Obesity, Linking PHIP Variants to Repressed POMC Transcription2020]

10/1/2019

Decreased from 3S to 1

New Scoring Scheme

Description

Reports Added

[New Scoring Scheme]

7/1/2019

Decreased from 3S to 3S

Description

Reports Added

[Clinical and genetic characterization of individuals with predicted deleterious PHIP variants.2019]

10/1/2017

Decreased from 4 to 3

Description

Reports Added

[Expanding the genetic heterogeneity of intellectual disability.2017] [Genomic Patterns of De Novo Mutation in Simplex Autism2017]

7/1/2017

Decreased from 4 to 4

Description

Reports Added

[Using medical exome sequencing to identify the causes of neurodevelopmental disorders: experience of two clinical units and 216 patients.2017]

4/1/2017

Decreased from 4 to 4

Description

Reports Added

[The contribution of de novo coding mutations to autism spectrum disorder2014] [De novo genic mutations among a Chinese autism spectrum disorder cohort.2016] [The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies.2016] [De novo PHIP-predicted deleterious variants are associated with developmental delay, intellectual disability, obesity, and dysmorphic features.2016] [Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases.2017] [A clinical utility study of exome sequencing versus conventional genetic testing in pediatric neurology.2017]

10/1/2016

Increased from to 4

Description

Krishnan Probability Score

Score 0.44718601258811

Ranking 13849/25841 scored genes

[Show Scoring Methodology]

Krishnan and colleagues generated probability scores genome-wide by using a machine learning approach on a human brain-specific gene network. The method was first presented in Nat Neurosci 19, 1454-1462 (2016), and scores for more than 25,000 RefSeq genes can be accessed in column G of supplementary table 3 (see: http://www.nature.com/neuro/journal/v19/n11/extref/nn.4353-S5.xlsx). A searchable browser, with the ability to view networks of associated ASD risk genes, can be found at asd.princeton.edu.

Original Source

ExAC Score

Score 0.99999994770165

Ranking 173/18225 scored genes

[Show Scoring Methodology]

The Exome Aggregation Consortium (ExAC) is a summary database of 60,706 exomes that has been widely used to estimate 'constraint' on mutation for individual genes. It was introduced by Lek et al. Nature 536, 285-291 (2016), and the ExAC browser can be found at exac.broadinstitute.org. The pLI score was developed as measure of intolerance to loss-of- function mutation. A pLI > 0.9 is generally viewed as highly constrained, and thus any loss-of- function mutations in autism in such a gene would be more likely to confer risk. For a full list of pLI scores see: ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3.1/functional_gene_constraint/fordist_cle aned_exac_nonTCGA_z_pli_rec_null_data.txt

Original Source

Sanders TADA Score

Score 0.94685804943982

Ranking 17040/18665 scored genes

[Show Scoring Methodology]

The TADA score ('Transmission and De novo Association') was introduced by He et al. PLoS Genet 9(8):e1003671 (2013), and is a statistic that integrates evidence from both de novo and transmitted mutations. It forms the basis for the claim of 65 individual genes being strongly associated with autism risk at a false discovery rate of 0.1 (Sanders et al. Neuron 87, 1215-1233 (2015)). The calculated TADA score for 18,665 RefSeq genes can be found in column P of Supplementary Table 6 in the Sanders et al. paper (the column headed 'tadaFdrAscSscExomeSscAgpSmallDel'), which represents a combined analysis of exome data and small de novo deletions (see www.cell.com/cms/attachment/2038545319/2052606711/mmc7.xlsx).

Original Source

Zhang D Score

Score 0.60580098224821

Ranking 71/20870 scored genes

[Show Scoring Methodology]

The DAMAGES score (disease-associated mutation analysis using gene expression signatures), or D score, was developed to combine evidence from de novo loss-of- function mutation with evidence from cell-type- specific gene expression in the mouse brain (specifically translational profiles of 24 specific mouse CNS cell types isolated from 6 different brain regions). Genes with positive D scores are more likely to be associated with autism risk, with higher-confidence genes having higher D scores. This statistic was first presented by Zhang & Shen (Hum Mutat 38, 204- 215 (2017), and D scores for more than 20,000 RefSeq genes can be found in column M in supplementary table 2 from that paper.

Original Source

Human Gene Module / Chromosome 6 / PHIP

PHIPpleckstrin homology domain interacting protein

SFARI Gene Score

Autism Reports / Total Reports

Rare Variants / Common Variants

Aliases

Associated Syndromes

Chromosome Band

Associated Disorders

Relevance to Autism

Molecular Function

External Links

Human

SFARI Genomic Platforms

Reports related to PHIP (28 Reports)

Rare Variants (136)

Common Variants

SFARI Gene score

High Confidence, Syndromic

Score Delta: Score remained at 1S

criteria met

High Confidence

Syndromic

1/1/2021

Score remained at 1

Description

Reports Added

10/1/2020

Score remained at 1

Description

Reports Added

7/1/2020

Score remained at 1

Description

Reports Added

10/1/2019

Decreased from 3S to 1

New Scoring Scheme

Description

Reports Added

7/1/2019

Decreased from 3S to 3S

Description

Reports Added

10/1/2017

Decreased from 4 to 3

Description

Reports Added

7/1/2017

Decreased from 4 to 4

Description

Reports Added

4/1/2017

Decreased from 4 to 4

Description

Reports Added

10/1/2016

Increased from to 4

Description

Krishnan Probability Score

Score 0.44718601258811

Ranking 13849/25841 scored genes

ExAC Score

Score 0.99999994770165

Ranking 173/18225 scored genes

Sanders TADA Score

Score 0.94685804943982

Ranking 17040/18665 scored genes

Zhang D Score

Score 0.60580098224821

Ranking 71/20870 scored genes