SRRM2

Chr 16AD

serine/arginine repetitive matrix 2

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

NCBI Gene: 23524 ENSG00000167978 UniProt: Q9UQ35 OMIM: 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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Enables C2H2 zinc finger domain binding activity. Involved in mRNA splicing, via spliceosome. Located in Cajal body and nuclear speck. Part of U2-type catalytic step 2 spliceosome and U2-type precatalytic spliceosome. Implicated in autosomal dominant intellectual developmental disorder 72. Biomarker of Parkinson's disease. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOFmechanismADLOEUF 0.121 OMIM phenotype

Clinical Summary— SRRM2

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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.

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ClinVar Variants

70 unique Pathogenic / Likely Pathogenic· 836 VUS of 1176 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 OE?0.06 (0.04–0.12)

0≤0.351.4

Missense OE?1.43 (1.38–1.48)

0≤0.61.4

Synonymous OE?1.67

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

This gene — mechanism propensity

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 · 99% of P/LP variants are LoF · LOEUF 0.12 · ClinGen HI: Sufficient evidence for dosage pathogenicity

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

1176 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic45

Likely Pathogenic25

VUS836

Likely Benign199

Benign20

Conflicting22

Pathogenic

Likely Pathogenic

836

VUS

199

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	45	0	0	0	45
Likely Pathogenic	24	1	0	0	25
VUS	7	823	6	0	836
Likely Benign	0	139	6	54	199
Benign	0	13	0	7	20
Conflicting	—				22
Total	76	976	12	61	1,147

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

View in ClinVar →

33 pathogenic / likely-pathogenic (of 46) ClinVar copy-number / structural variants overlap SRRM2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →