STARD4

Chr 5

StAR related lipid transfer domain containing 4

Cholesterol homeostasis is regulated, at least in part, by sterol regulatory element (SRE)-binding proteins (e.g., SREBP1; MIM 184756) and by liver X receptors (e.g., LXRA; MIM 602423). Upon sterol depletion, LXRs are inactive and SREBPs are cleaved, after which they bind promoter SREs and activate genes involved in cholesterol biosynthesis and uptake. Sterol transport is mediated by vesicles or by soluble protein carriers, such as steroidogenic acute regulatory protein (STAR; MIM 600617). STAR is homologous to a family of proteins containing a 200- to 210-amino acid STAR-related lipid transfer (START) domain, including STARD4 (Soccio et al., 2002 [PubMed 12011452]).[supplied by OMIM, Mar 2008]

ResearchGenerating clinical summary…
GOFmechanismLOEUF 1.82
Clinical SummarySTARD4
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
23 VUS of 26 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
1.82LOEUF
pLI 0.000
Z-score -0.76
OE 1.24 (0.811.82)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?
0.66Z-score
OE missense 0.82 (0.700.98)
93 obs / 112.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?1.24 (0.811.82)
00.351.4
Missense OE?0.82 (0.700.98)
00.61.4
Synonymous OE?0.96
01.21.6
LoF obs/exp: 14 / 11.3Missense obs/exp: 93 / 112.8Syn Z: 0.19

This gene — mechanism propensity

DN
0.4487th %ile
GOF
0.6344th %ile
LOF
0.3552th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction 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

26 submitted variants in ClinVar

Classification Summary

VUS23
23
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
0
0
0
Likely Pathogenic
0
0
0
0
0
VUS
0
23
0
0
23
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total0230023

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

View in ClinVar →

25 pathogenic / likely-pathogenic (of 31) ClinVar copy-number / structural variants overlap STARD4 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

STARD4 · 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 →