SRRM2

Chr 16AD

serine/arginine repetitive matrix 2

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

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]

OMIMResearchGenerating clinical summary…
LOFmechanismADLOEUF 0.121 OMIM phenotype
Clinical SummarySRRM2
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
70 unique Pathogenic / Likely Pathogenic· 836 VUS of 1176 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint?
0.12LOEUF
pLI 1.000
Z-score 9.17
OE 0.06 (0.040.12)
Highly constrained

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

Missense Constraint?
-6.28Z-score
OE missense 1.43 (1.381.48)
2410 obs / 1684.4 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?0.06 (0.040.12)
00.351.4
Missense OE?1.43 (1.381.48)
00.61.4
Synonymous OE?1.67
01.21.6
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

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 · 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

Classification Summary

Pathogenic45
Likely Pathogenic25
VUS836
Likely Benign199
Benign20
Conflicting22
45
Pathogenic
25
Likely Pathogenic
836
VUS
199
Likely Benign
20
Benign
22
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
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
Total7697612611,147

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 →

Protein Context — Lollipop Plot

SRRM2 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →