SRRM2

Chr 16AD

serine/arginine repetitive matrix 2

Also known as: 300-KD, CWF21, Cwc21, HSPC075, MRD72, SRL300, SRm300

NCBI Gene: 23524ENSG00000167978UniProt: Q9UQ35OMIM: 606032

The protein is required for pre-mRNA splicing as a component of both major and minor spliceosomes, participating in the removal of introns from pre-mRNAs. Mutations cause intellectual developmental disorder, autosomal dominant 72, following an autosomal dominant inheritance pattern. The gene is highly constrained against loss-of-function mutations (pLI ~1.0, LOEUF 0.118), indicating that functional copies are essential for normal development.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.121 OMIM phenotype
Clinical Summary— SRRM2
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
18 unique Pathogenic / Likely Pathogenic· 202 VUS of 300 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.12LOEUF
pLI 1.000
Z-score 9.17
OE 0.06 (0.04–0.12)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
-6.28Z-score
OE missense 1.43 (1.38–1.48)
2410 obs / 1684.4 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.06 (0.04–0.12)
0≤0.351.4
Missense OE1.43 (1.38–1.48)
0≤0.61.4
Synonymous OE1.67
0≤1.21.6
LoF obs/exp: 7 / 111.4Missense obs/exp: 2410 / 1684.4Syn Z: -13.16
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveSRRM2-related developmental disorderLOFAD
DN
0.2698th %ile
GOF
0.2696th %ile
LOF
0.79top 5%

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

LOFprediction above median · 94% of P/LP variants are LoF · LOEUF 0.12

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

300 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic9
Likely Pathogenic9
VUS202
Likely Benign48
Benign1
Conflicting2
9
Pathogenic
9
Likely Pathogenic
202
VUS
48
Likely Benign
1
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
8
0
1
0
9
Likely Pathogenic
9
0
0
0
9
VUS
1
201
0
0
202
Likely Benign
0
31
1
16
48
Benign
0
1
0
0
1
Conflicting
—2
Total18233216271

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

View in ClinVar →

Protein Context — Lollipop Plot

SRRM2 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients