SIM1

Chr 6

SIM bHLH transcription factor 1

Also known as: bHLHe14

NCBI Gene: 6492ENSG00000112246UniProt: P81133

SIM1 and SIM2 genes are Drosophila single-minded (sim) gene homologs. SIM1 transcript was detected only in fetal kidney out of various adult and fetal tissues tested. Since the sim gene plays an important role in Drosophila development and has peak levels of expression during the period of neurogenesis,it was proposed that the human SIM gene is a candidate for involvement in certain dysmorphic features (particularly the facial and skull characteristics), abnormalities of brain development, and/or cognitive disability of Down syndrome. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.
4
Active trials
24
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.25
LOEUF· LoF intol.
LOF
Mechanism· G2P
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?
0.25LOEUF
pLI 0.998
Z-score 4.96
OE 0.11 (0.05–0.25)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
0.71Z-score
OE missense 0.90 (0.83–0.98)
405 obs / 447.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.11 (0.05–0.25)
0≤0.351.4
Missense OE?0.90 (0.83–0.98)
0≤0.61.4
Synonymous OE?1.03
0≤1.21.6
LoF obs/exp: 4 / 36.2Missense obs/exp: 405 / 447.6Syn Z: -0.31

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

SIM1 · protein map & ClinVar variants

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

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