SNIP1

Chr 1AR

Smad nuclear interacting protein 1

Also known as: NEDHCS, PML1, PMRED

NCBI Gene: 79753ENSG00000163877UniProt: Q8TAD8

This gene encodes a protein that contains a coiled-coil motif and C-terminal forkhead-associated (FHA) domain. The encoded protein functions as a transcriptional coactivator that increases c-Myc activity and inhibits transforming growth factor beta (TGF-beta) and nuclear factor kappa-B (NF-kB) signaling. The encoded protein also regulates the stability of cyclin D1 mRNA, and may play a role in cell proliferation and cancer progression. Mutations in this gene are a cause of psychomotor retardation, epilepsy, and craniofacial dysmorphism (PMRED). [provided by RefSeq, Mar 2012]

Primary Disease Associations & Inheritance

Neurodevelopmental disorder with hypotonia, craniofacial abnormalities, and seizuresMIM #614501
AR
283
ClinVar variants
6
Pathogenic / LP
0.42
pLI score
0
Active trials
Clinical Summary— SNIP1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.22) despite low pLI — interpret in context.
📋
ClinVar Variants
6 Pathogenic / Likely Pathogenic· 182 VUS of 283 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.50LOEUF
pLI 0.422
Z-score 3.10
OE 0.22 (0.11–0.50)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.24Z-score
OE missense 0.78 (0.70–0.88)
201 obs / 256.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.22 (0.11–0.50)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.78 (0.70–0.88)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.83
0≤1.21.6
LoF obs/exp: 4 / 18.3Missense obs/exp: 201 / 256.8Syn Z: 1.26

ClinVar Variant Classifications

283 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4
Likely Pathogenic2
VUS182
Likely Benign80
Benign7
Conflicting8
4
Pathogenic
2
Likely Pathogenic
182
VUS
80
Likely Benign
7
Benign
8
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
4
0
4
Likely Pathogenic
0
0
2
0
2
VUS
4
154
24
0
182
Likely Benign
0
5
15
60
80
Benign
0
1
2
4
7
Conflicting
—8
Total41604764283

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SNIP1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

SNIP1-related symptomatic epilepsy and skull dysplasia

limited
ARUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Neurodevelopmental disorder with hypotonia, craniofacial abnormalities, and seizures

MIM #614501

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — SNIP1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
TET2 suppresses vascular calcification by forming an inhibitory complex with HDAC1/2 and SNIP1 independent of demethylation.
He D et al.·J Clin Invest
2025
Long non-coding RNA AFAP1-AS1 accelerates lung cancer cells migration and invasion by interacting with SNIP1 to upregulate c-Myc.
Zhong Y et al.·Signal Transduct Target Ther
2021
The SWI/SNF chromatin remodeling factor DPF3 regulates metastasis of ccRCC by modulating TGF-β signaling.
Cui H et al.·Nat Commun
2022Functional
MKRN1 promotes colorectal cancer metastasis by activating the TGF-β signalling pathway through SNIP1 protein degradation.
Zhang Y et al.·J Exp Clin Cancer Res
2023
A biallelic SNIP1 Amish founder variant causes a recognizable neurodevelopmental disorder.
Ammous Z et al.·PLoS Genet
2021
Functional analysis of the 1p34.3 risk locus implicates GNL2 in high-grade serous ovarian cancer.
Nakamura K et al.·Am J Hum Genet
2022Functional
Psychosis Biotypes: Replication and Validation from the B-SNIP Consortium.
Clementz BA et al.·Schizophr Bull
2022
Auditory Oddball Responses Across the Schizophrenia-Bipolar Spectrum and Their Relationship to Cognitive and Clinical Features.
Parker DA et al.·Am J Psychiatry
2021
Regulation of ATR-dependent pathways by the FHA domain containing protein SNIP1.
Roche KC et al.·Oncogene
2007
Identification of an individualized RNA binding protein-based prognostic signature for diffuse large B-cell lymphoma.
Xie Y et al.·Cancer Med
2021
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools