STARD3

protein-coding

StAR related lipid transfer domain containing 3, the group of StAR related lipid transfer domain containing

Gene summary

This gene encodes a member of a subfamily of lipid trafficking proteins that are characterized by a C-terminal steroidogenic acute regulatory domain and an N-terminal metastatic lymph node 64 domain. The encoded protein localizes to the membranes of late endosomes and may be involved in exporting cholesterol. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Oct 2009]

MANE transcript

NM_006804.4

Inheritance

—

ClinVar variants

U:69B:8

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.41

Max pathogenic AF

—

Genomic locus

chr17:39,637,090-39,664,201

External References & Databases

Ensembl (ENSG00000131748)

Transcript & Mutation Effects

hg38 • Region Span ~27.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to STARD3 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 64

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006804.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	3 clinvar	1 clinvar	5
missense			62 clinvar	4 clinvar		66
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	0	69	7	1	77

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 115 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006804.4	RefSeq	NP_006795.3	14	MANE Select
ENST00000336308.10	Ensembl	ENSP00000337446.5	14	MANE Select
NM_001165937.2	RefSeq	NP_001159409.1	14	Standard
NM_001165938.2	RefSeq	NP_001159410.1	13	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Cholesterol metabolism - Homo sapiens (human)
Metabolism of lipids
Metabolism
Pregnenolone biosynthesis
Metabolism of steroid hormones

Biological Process

lipid metabolic process
C21-steroid hormone biosynthetic process
progesterone biosynthetic process
mitochondrial transport
steroid metabolic process

Molecular Function

protein binding
cholesterol binding
cholesterol transporter activity
protein homodimerization activity

Cellular Component

cytoplasm
mitochondrion
lysosomal membrane
endoplasmic reticulum membrane
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000336308
Coding exons: 14
Length: 26420
Individuals with no LoFs: 125719
Homozygous LoFs: 0
Heterozygous LoFs: 27
Defined: 125746
p: 0.000107

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.906	241	284	0.849	0.0000190	2849
Missense (PolyPhen)		87	99.612	0.87339		992
Synonymous	-0.767	128	117	1.09	0.00000761	911
Loss of Function	2.95	12	29.2	0.411	0.00000167	294

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00013	0.00013	rare
South Asian	0.00013	0.00013	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Sterol-binding protein that mediates cholesterol transport from the endoplasmic reticulum to endosomes (PubMed:11053434, PubMed:15930133, PubMed:22514632, PubMed:28377464). Creates contact site between the endoplasmic reticulum and late endosomes: localizes to late endosome membranes and contacts the endoplasmic reticulum via interaction with VAPA and VAPB (PubMed:24105263, PubMed:28377464). Acts as a lipid transfer protein that redirects sterol to the endosome at the expense of the cell membrane and favors membrane formation inside endosomes (PubMed:28377464). May also mediate cholesterol transport between other membranes, such as mitochondria membrane or cell membrane (PubMed:12070139, PubMed:19965586). However, such results need additional experimental evidences; probably mainly mediates cholesterol transport from the endoplasmic reticulum to endosomes (PubMed:28377464). Does not activate transcriptional cholesterol sensing (PubMed:28377464). Able to bind other lipids, such as lutein, a xanthophyll carotenoids that form the macular pigment of the retina (PubMed:21322544). {ECO:0000269|PubMed:11053434, ECO:0000269|PubMed:12070139, ECO:0000269|PubMed:15930133, ECO:0000269|PubMed:19965586, ECO:0000269|PubMed:21322544, ECO:0000269|PubMed:22514632, ECO:0000269|PubMed:24105263, ECO:0000269|PubMed:28377464}.;

Recessive Scores

pRec: 0.152

Intolerance Scores

LoFtool: 0.0559
RVIS EVS: -0.24
RVIS percentile EVS: 36.17

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.584

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High