SNRPD1

Chr 18

small nuclear ribonucleoprotein D1 polypeptide

Also known as: HsT2456, SMD1, SNRPD, Sm-D1

The protein is a core component of small nuclear ribonucleoproteins (snRNPs) that are essential building blocks of the spliceosome, functioning in pre-mRNA splicing of both major and minor (U12-type) introns. Mutations cause autosomal recessive neurodevelopmental disorders with early childhood onset, typically involving intellectual disability, seizures, and brain malformations. The gene is highly constrained against loss-of-function variants (LOEUF 0.564), reflecting the critical importance of proper splicing for normal development.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
2
Pubs (1 yr)
33
P/LP submissions
P/LP missense
0.56
LOEUF
LOF
Mechanism· predicted
Clinical SummarySNRPD1
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.80) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
31 unique Pathogenic / Likely Pathogenic· 11 VUS of 51 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.56LOEUF
pLI 0.799
Z-score 2.14
OE 0.00 (0.000.56)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.29Z-score
OE missense 0.22 (0.150.34)
15 obs / 68.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.00 (0.000.56)
00.351.4
Missense OE0.22 (0.150.34)
00.61.4
Synonymous OE0.73
01.21.6
LoF obs/exp: 0 / 5.3Missense obs/exp: 15 / 68.4Syn Z: 1.02
DN
0.4388th %ile
GOF
0.2298th %ile
LOF
0.83top 5%

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

LOFprediction above median

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

51 submitted variants in ClinVar

Classification Summary

Pathogenic30
Likely Pathogenic1
VUS11
30
Pathogenic
1
Likely Pathogenic
11
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
30
Likely Pathogenic
1
VUS
11
Likely Benign
0
Benign
0
Total42

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SNRPD1 · 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 →
Clinical Literature
Open Research Assistant →