Human Gene Module / Chromosome 7 / MKRN1

MKRN1makorin ring finger protein 1

SFARI Gene Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
3 / 4
Rare Variants / Common Variants
4 / 0
Aliases
-
Associated Syndromes
-
Chromosome Band
7q34
Associated Disorders
-
Relevance to Autism

Functional assessment of de novo 5'UTR variants identified in ASD probands from the Simons Simplex Collection (SSC) by massively parallel reporter assay (MPRA) using polysomes from cell lines in Plassmeyer et al., 2025 reported an ASD-associated 5'UTR variant in the MKRN1 gene that resulted in reduced relative polysome/80S enrichment in both in cellulo MRPA studies in HEK cells and in patient-derived LCLs, as well as reduced protein expression in patient-derived LCLs and in a dual-luciferase reporter assay (FDR-adjusted p-value < 0.05). A de novo missense variant with a CADD score > 30 was identified in a female ASD proband from the SPARK cohort (Zhou et al., 2022). Rare deletions affecting the MKRN1 gene (defined as those found in <0.1% of 10,851 population control samples) were identified in two individuals diagnosed with ASD and one diagnosed with schizophrenia from a cohort of 2,691 subjects diagnosed with a neurodevelopmental disorder (Zarrei et al., 2019).

Molecular Function

This gene encodes a protein that belongs to a novel class of zinc finger proteins. The encoded protein functions as a transcriptional co-regulator, and as an E3 ubiquitin ligase that promotes the ubiquitination and proteasomal degradation of target proteins. The protein encoded by this gene is thought to regulate RNA polymerase II-catalyzed transcription. Substrates for this protein's E3 ubiquitin ligase activity include the capsid protein of the West Nile virus and the catalytic subunit of the telomerase ribonucleoprotein. This protein controls cell cycle arrest and apoptosis by regulating p21, a cell cycle regulator, and the tumor suppressor protein p53. Fang et al., 2021 found that MKRN1 interacted with and regulated degradation of the neuron-specific Eag1 voltage-gated potassium channel encoded by the KCNH1 gene.

External Links
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Human
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SFARI Genomic Platforms
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Reports related to MKRN1 (4 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support - Mehdi Zarrei et al. (2019) Yes -
2 Support - Ya-Ching Fang et al. (2021) No -
3 Support - Zhou X et al. (2022) Yes -
4 Primary - Stephen P Plassmeyer et al. (2025) Yes -
Rare Variants   (4)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_loss Unknown - Unknown 31602316 Mehdi Zarrei et al. (2019)
- - copy_number_loss Unknown - Multiplex 31602316 Mehdi Zarrei et al. (2019)
c.227G>A p.Arg76His missense_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.-231_-228dup - 5_prime_UTR_variant De novo - Simplex 41344325 Stephen P Plassmeyer et al. (2025)
Common Variants  

No common variants reported.

SFARI Gene score
3

Suggestive Evidence

Score Delta: Score remained at 3

criteria met
See SFARI Gene'scoring criteria
3

Suggestive Evidence

See all Category 3 Genes

The literature is replete with relatively small studies of candidate genes, using either common or rare variant approaches, which do not reach the criteria set out for categories 1 and 2. Genes that had two such lines of supporting evidence were placed in category 3, and those with one line of evidence were placed in category 4. Some additional lines of "accessory evidence" (indicated as "acc" in the score cards) could also boost a gene from category 4 to 3.

10/1/2025
icon
3

Increased from to 3

Krishnan Probability Score

Score 0.45474898879565

Ranking 10126/25841 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 0.97942365116225

Ranking 2151/18225 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 0.82993820994325

Ranking 2849/18665 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 0.42651962492957

Ranking 1158/20870 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
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