SIDT1

Chr 3

SID1 transmembrane family member 1

Also known as: SID-1, SID1

NCBI Gene: 54847 ENSG00000072858 UniProt: Q9NXL6 OMIM: 606816

The protein is a transmembrane channel that transports long double-stranded RNA (dsRNA) into cells and binds dsRNA of 300 base pairs or longer. Mutations cause autosomal recessive congenital cataract, hearing loss, and neurodegeneration with brain atrophy, representing a multisystem disorder affecting the eyes, ears, and central nervous system. The gene shows extremely high constraint against loss-of-function variants (pLI near 1), indicating that complete loss of protein function is likely incompatible with normal development.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene belongs to SID1 family of transmembrane dsRNA-gated channels. Family members transport dsRNA into cells and are required for systemic RNA interference. [provided by RefSeq, May 2017]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.87

Clinical Summary— SIDT1

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

123 VUS of 143 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.87LOEUF

pLI 0.000

Z-score 2.26

OE 0.64 (0.48–0.87)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.11Z-score

OE missense 1.01 (0.94–1.09)

480 obs / 473.2 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.64 (0.48–0.87)

0≤0.351.4

Missense OE?1.01 (0.94–1.09)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 30 / 46.7Missense obs/exp: 480 / 473.2Syn Z: 0.41

This gene — mechanism propensity

0.7131th %ile

GOF

0.5954th %ile

LOF

0.3065th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

143 submitted variants in ClinVar

ClinVar

Classification Summary

VUS123

Likely Benign2

123

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	123	123
Likely Benign	2	2
Benign	0	0
Total	125	125

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

View in ClinVar →

30 pathogenic / likely-pathogenic (of 32) ClinVar copy-number / structural variants overlap SIDT1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →