SRRM4

Chr 12

serine/arginine repetitive matrix 4

Also known as: KIAA1853, MU-MB-2.76, nSR100

The protein functions as a splicing factor that promotes neural-specific exon inclusion and is specifically required for neural cell differentiation. Mutations cause neurodevelopmental disorders with intellectual disability, developmental delay, and seizures, with some patients showing autism spectrum disorder features. The gene follows autosomal recessive inheritance and is highly constrained against loss-of-function mutations.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.41
Clinical SummarySRRM4
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.22) despite low pLI — interpret in context.
📋
ClinVar Variants
14 unique Pathogenic / Likely Pathogenic· 95 VUS of 118 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.41LOEUF
pLI 0.465
Z-score 4.10
OE 0.22 (0.120.41)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.39Z-score
OE missense 0.80 (0.730.88)
311 obs / 388.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.22 (0.120.41)
00.351.4
Missense OE0.80 (0.730.88)
00.61.4
Synonymous OE0.98
01.21.6
LoF obs/exp: 7 / 32.0Missense obs/exp: 311 / 388.2Syn Z: 0.21
DN
0.5181th %ile
GOF
0.4874th %ile
LOF
0.66top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.41

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

118 submitted variants in ClinVar

Classification Summary

Pathogenic9
Likely Pathogenic5
VUS95
Likely Benign4
9
Pathogenic
5
Likely Pathogenic
95
VUS
4
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
9
0
9
Likely Pathogenic
0
0
5
0
5
VUS
1
91
3
0
95
Likely Benign
0
4
0
0
4
Benign
0
0
0
0
0
Total195170113

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

View in ClinVar →

Protein Context — Lollipop Plot

SRRM4 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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