STARD8

Summary

STARD8 (StAR related lipid transfer domain containing 8, HGNC:19161) is a protein-coding gene on chromosome Xq13.1, encoding StAR-related lipid transfer protein 8 (Q92502). Accelerates GTPase activity of RHOA and CDC42, but not RAC1.

This gene encodes a member of a subfamily of Rho GTPase activating proteins that contain a steroidogenic acute regulatory protein related lipid transfer domain. The encoded protein localizes to focal adhesions and may be involved in regulating cell morphology. This protein may also function as a tumor suppressor.

Source: NCBI Gene 9754 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 222 total
• MANE Select transcript: NM_001142503

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19161
Approved symbol	STARD8
Name	StAR related lipid transfer domain containing 8
Location	Xq13.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0189, ARHGAP38
Ensembl gene	ENSG00000130052
Ensembl biotype	protein_coding
OMIM	300689
Entrez	9754

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000252336, ENST00000374597, ENST00000374599, ENST00000488088, ENST00000523864

RefSeq mRNA: 3 — MANE Select: NM_001142503 NM_001142503, NM_001142504, NM_014725

CCDS: CCDS14390, CCDS48134

Canonical transcript exons

ENST00000374599 — 15 exons

Exon	Start	End
ENSE00002108518	68724305	68725836
ENSE00002128470	68647666	68647927
ENSE00003474070	68721536	68721746
ENSE00003474097	68665499	68665532
ENSE00003491236	68722047	68722161
ENSE00003516364	68720264	68720423
ENSE00003538862	68722422	68722646
ENSE00003544300	68720924	68721122
ENSE00003572245	68717212	68718629
ENSE00003614614	68716368	68716431
ENSE00003658034	68712914	68712985
ENSE00003662085	68723626	68723843
ENSE00003670755	68719225	68719398
ENSE00003671911	68715294	68715375
ENSE00003682043	68723945	68724121

Expression profiles

Bgee: expression breadth ubiquitous, 219 present calls, max score 89.35.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.0341 / max 179.7160, expressed in 1185 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
196592	8.5775	1173
196593	0.4566	219

Top tissues by expression

273 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lung	UBERON:0002167	89.35	gold quality
diaphragm	UBERON:0001103	87.76	gold quality
upper lobe of left lung	UBERON:0008952	86.93	gold quality
metanephros cortex	UBERON:0010533	86.37	gold quality
apex of heart	UBERON:0002098	86.27	gold quality
upper lobe of lung	UBERON:0008948	86.08	gold quality
olfactory bulb	UBERON:0002264	84.88	silver quality
type B pancreatic cell	CL:0000169	84.48	gold quality
gluteal muscle	UBERON:0002000	84.28	silver quality
adult mammalian kidney	UBERON:0000082	83.62	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.02	gold quality
omental fat pad	UBERON:0010414	83.01	gold quality
peritoneum	UBERON:0002358	82.96	gold quality
adipose tissue of abdominal region	UBERON:0007808	82.19	gold quality
lung	UBERON:0002048	81.74	gold quality
heart left ventricle	UBERON:0002084	81.32	gold quality
right lobe of thyroid gland	UBERON:0001119	81.29	gold quality
cardiac ventricle	UBERON:0002082	81.15	gold quality
metanephros	UBERON:0000081	80.65	gold quality
kidney	UBERON:0002113	80.29	gold quality
left uterine tube	UBERON:0001303	80.20	gold quality
left lobe of thyroid gland	UBERON:0001120	79.94	gold quality
mucosa of stomach	UBERON:0001199	79.71	gold quality
cortex of kidney	UBERON:0001225	79.66	gold quality
subcutaneous adipose tissue	UBERON:0002190	79.56	gold quality
tibial nerve	UBERON:0001323	79.49	gold quality
spleen	UBERON:0002106	79.48	gold quality
heart	UBERON:0000948	79.07	gold quality
right atrium auricular region	UBERON:0006631	78.94	gold quality
body of uterus	UBERON:0009853	78.87	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.87

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

65 targeting STARD8, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-580-3P	99.67	69.23	1841
HSA-MIR-6752-5P	99.59	67.32	1243

Literature-anchored findings (GeneRIF, showing 6)

• DLC3 is recruited to Rab8-positive membrane tubules and is required for the integrity of the Rab8 and Golgi compartments. (PMID:25673874)
• a new function for Scribble in Rho regulation that entails positioning of DLC3 GAP activity at cell junctions in polarized epithelial cells, is reported. (PMID:27505894)
• The authors propose that DLC3 function is required to limit endosomal actin polymerization, Rab4-dependent recycling of MT1-MMP and, consequently, matrix degradation mediated by invadopodial activity. (PMID:31076513)
• A conserved function of Human DLC3 and Drosophila Cv-c in testis development. (PMID:36326091)
• PYCR1, BANF1, and STARD8 Expression in Gastric Carcinoma: A Clinicopathologic, Prognostic, and Immunohistochemical Study. (PMID:37982568)
• Regional bias of tumor suppressor gene mutations of STARD8 and WNK2 in colon cancers. (PMID:38091885)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	stard8	ENSDARG00000014003
mus_musculus	Stard8	ENSMUSG00000031216
rattus_norvegicus	Stard8	ENSRNOG00000033883
caenorhabditis_elegans		WBGENE00001559

Paralogs (2): STARD13 (ENSG00000133121), DLC1 (ENSG00000164741)

Protein

Protein identifiers

StAR-related lipid transfer protein 8 — Q92502 (reviewed: Q92502)

Alternative names: Deleted in liver cancer 3 protein, START domain-containing protein 8, START-GAP3

All UniProt accessions (2): Q92502, E5RFN7

UniProt curated annotations — full annotation on UniProt →

Function. Accelerates GTPase activity of RHOA and CDC42, but not RAC1. Stimulates the hydrolysis of phosphatidylinositol 4,5-bisphosphate by PLCD1.

Subunit / interactions. Binds both the SH2 and PTB domains of TNS1.

Subcellular location. Cell junction. Focal adhesion.

Tissue specificity. Widely expressed with highest levels in kidney, lung and placenta.

Isoforms (2)

UniProt ID	Names	Canonical?
Q92502-1	1, DLC3beta	yes
Q92502-2	2, DLC3alpha

RefSeq proteins (3): NP_001135975, NP_001135976, NP_055540 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000198	RhoGAP_dom	Domain
IPR002913	START_lipid-bd_dom	Domain
IPR008936	Rho_GTPase_activation_prot	Homologous_superfamily
IPR023393	START-like_dom_sf	Homologous_superfamily

Pfam: PF00620, PF01852

UniProt features (27 total): modified residue 6, compositionally biased region 5, region of interest 5, sequence variant 3, domain 2, sequence conflict 2, chain 1, site 1, splice variant 1, mutagenesis site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92502-F1	63.19	0.38

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 608 (arginine finger; crucial for gtp hydrolysis by stabilizing the transition state)

Post-translational modifications (6): 108, 169, 235, 238, 498, 506

Mutagenesis-validated functional residues (1):

Position	Phenotype
608	no effect on cell morphology when overexpressed.

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-8980692	RHOA GTPase cycle
R-HSA-9013026	RHOB GTPase cycle
R-HSA-9013148	CDC42 GTPase cycle
R-HSA-162582	Signal Transduction
R-HSA-194315	Signaling by Rho GTPases
R-HSA-9012999	RHO GTPase cycle
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 147 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, WTGAAAT_UNKNOWN, TGANTCA_AP1_C, GOBP_REGULATION_OF_RHO_PROTEIN_SIGNAL_TRANSDUCTION, NKX22_01, TGGNNNNNNKCCAR_UNKNOWN, CUI_TCF21_TARGETS_2_DN, IK3_01, GOBP_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, NERF_Q2, P53_DECAMER_Q2, TTCNRGNNNNTTC_HSF_Q6, RIGGINS_TAMOXIFEN_RESISTANCE_UP, GOCC_ANCHORING_JUNCTION

GO Biological Process (3): signal transduction (GO:0007165), actin cytoskeleton organization (GO:0030036), regulation of Rho protein signal transduction (GO:0035023)

GO Molecular Function (2): GTPase activator activity (GO:0005096), lipid binding (GO:0008289)

GO Cellular Component (2): focal adhesion (GO:0005925), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
RHO GTPase cycle	3
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signaling by Rho GTPases	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cytoskeleton organization	1
actin filament-based process	1
Rho protein signal transduction	1
regulation of small GTPase mediated signal transduction	1
GTPase activity	1
enzyme activator activity	1
GTPase regulator activity	1
binding	1
cell-substrate junction	1
cell junction	1

Protein interactions and networks

STRING

827 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
STARD8	YIPF6	Q96EC8	840
STARD8	PLCD1	P51178	748
STARD8	RHOA	P06749	623
STARD8	STARD6	P59095	580
STARD8	STARD5	P59094	577
STARD8	STAR	P49675	559
STARD8	TNS3	Q68CZ2	555
STARD8	PCTP	Q9UKL6	553
STARD8	STARD7	Q9NQZ5	551
STARD8	STARD9	Q9P2P6	543
STARD8	CERT1	Q9Y5P4	543
STARD8	STARD10	Q9Y365	537
STARD8	TNS2	Q63HR2	531
STARD8	TNS4	Q8IZW8	529
STARD8	STARD3	Q14849	524

IntAct

7 interactions, top by confidence:

A	B	Type	Score
STARD8	JPH1	psi-mi:“MI:0914”(association)	0.530
SCRIB	STARD8	psi-mi:“MI:0915”(physical association)	0.400
TNS1	STARD8	psi-mi:“MI:0915”(physical association)	0.400
STARD8	PPP3CC	psi-mi:“MI:0914”(association)	0.350
STARD8	KANK2	psi-mi:“MI:0914”(association)	0.350

BioGRID (21): STARD8 (Affinity Capture-RNA), STARD8 (FRET), STARD8 (FRET), JPH1 (Affinity Capture-MS), KRT84 (Affinity Capture-MS), ABCD3 (Affinity Capture-MS), ATP5C1 (Affinity Capture-MS), TMEM263 (Affinity Capture-MS), HAX1 (Affinity Capture-MS), NSRP1 (Affinity Capture-MS), PRDX3 (Affinity Capture-MS), RPL22L1 (Affinity Capture-MS), SLIRP (Affinity Capture-MS), SNRPE (Affinity Capture-MS), ANKRD52 (Affinity Capture-MS)

ESM2 similar proteins: A2VDW6, A4D2P6, A8VU90, B0BNK9, E9PY61, F1LQY6, O94810, O95382, Q05AA6, Q0QWG9, Q13474, Q2TBQ9, Q3KR56, Q3UFQ8, Q3UR97, Q3V3V9, Q5FVC2, Q5R8E2, Q5XHY1, Q60875, Q61085, Q6F5E8, Q6P597, Q6P5Z2, Q6PRD1, Q6V7V2, Q80XL1, Q80ZJ8, Q865S3, Q86UD0, Q8C6B2, Q8K031, Q8K045, Q8N4Y2, Q8ND23, Q91W40, Q91ZP9, Q92502, Q92974, Q969H4

Diamond homologs: A0A0G2JTR4, A2AB59, A2RUV4, A4IF90, A4II46, A6QNS3, A6X8Z5, A7E300, A7KAX9, A8WRJ2, B2RTY4, D3ZZN9, E7EZG2, E7F3F0, F1LXF1, O14559, O43182, O54834, O74360, O94988, P11274, P15882, P30337, P34288, P42331, P46941, P52757, P98171, Q03070, Q08DP6, Q10164, Q12979, Q13459, Q15311, Q17QN0, Q20498, Q2M1Z3, Q3UIA2, Q53QZ3, Q54FG5

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
STARD8	“down-regulates activity”	RHOA	“gtpase-activating protein”
STARD8	“down-regulates activity”	CDC42	“gtpase-activating protein”

Disease & clinical

Clinical variants and AI predictions

ClinVar

222 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	136
Likely benign	18
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

3225 predictions. Top by Δscore:

Variant	Effect	Δscore
X:68647925:AAGGT:A	donor_loss	1.0000
X:68647926:AGGT:A	donor_loss	1.0000
X:68647927:GGTA:G	donor_loss	1.0000
X:68647928:G:GG	donor_gain	1.0000
X:68647928:GTAA:G	donor_loss	1.0000
X:68665496:CAGT:C	acceptor_loss	1.0000
X:68665497:A:AG	acceptor_gain	1.0000
X:68665497:AG:A	acceptor_loss	1.0000
X:68665497:AGT:A	acceptor_gain	1.0000
X:68665498:G:GT	acceptor_gain	1.0000
X:68665498:GT:G	acceptor_gain	1.0000
X:68665498:GTG:G	acceptor_gain	1.0000
X:68665498:GTGC:G	acceptor_gain	1.0000
X:68712901:T:TA	acceptor_gain	1.0000
X:68712906:T:TA	acceptor_gain	1.0000
X:68712908:TTTTA:T	acceptor_loss	1.0000
X:68712909:TTTAG:T	acceptor_loss	1.0000
X:68712910:TTAGA:T	acceptor_loss	1.0000
X:68712911:TAG:T	acceptor_loss	1.0000
X:68712912:A:AG	acceptor_gain	1.0000
X:68712913:G:C	acceptor_loss	1.0000
X:68712913:G:GG	acceptor_gain	1.0000
X:68712913:GA:G	acceptor_gain	1.0000
X:68712913:GAA:G	acceptor_gain	1.0000
X:68712986:G:T	donor_loss	1.0000
X:68712987:T:G	donor_loss	1.0000
X:68714574:T:G	donor_gain	1.0000
X:68714574:T:TG	donor_gain	1.0000
X:68719363:G:GT	donor_gain	1.0000
X:68719388:GGC:G	donor_gain	1.0000

AlphaMissense

7199 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:68721665:T:C	M713T	1.000
X:68720933:T:C	F607L	0.999
X:68720934:T:C	F607S	0.999
X:68720935:C:A	F607L	0.999
X:68720935:C:G	F607L	0.999
X:68720936:C:A	R608S	0.999
X:68721036:C:A	A641D	0.999
X:68721038:G:C	D642H	0.999
X:68721042:T:C	L643P	0.999
X:68721047:A:G	K645E	0.999
X:68721049:G:C	K645N	0.999
X:68721049:G:T	K645N	0.999
X:68721602:G:C	R692P	0.999
X:68721620:T:C	L698P	0.999
X:68721665:T:G	M713R	0.999
X:68721680:T:C	L718P	0.999
X:68721688:T:C	C721R	0.999
X:68721692:T:C	L722P	0.999
X:68722124:T:C	L766P	0.999
X:68723725:T:A	W887R	0.999
X:68723725:T:C	W887R	0.999
X:68720927:G:C	G605R	0.998
X:68720928:G:A	G605D	0.998
X:68720934:T:G	F607C	0.998
X:68720937:G:C	R608P	0.998
X:68720970:T:C	L619P	0.998
X:68720973:G:C	R620P	0.998
X:68721039:A:C	D642A	0.998
X:68721039:A:G	D642G	0.998
X:68721039:A:T	D642V	0.998

dbSNP variants (sampled 300 via entrez): RS1000135820 (X:68652078 G>A,C,T), RS1000141396 (X:68725343 T>C), RS1000242080 (X:68660867 C>A,T), RS1000305176 (X:68706878 T>G), RS1000315528 (X:68688332 C>A,T), RS1000326339 (X:68717967 T>C), RS1000365227 (X:68717997 G>A), RS1000370055 (X:68709726 G>C), RS1000374499 (X:68676228 G>A,C), RS1000378524 (X:68653086 C>A,G,T), RS1000391882 (X:68700668 T>C), RS1000475522 (X:68649924 A>C), RS1000504790 (X:68705364 T>C), RS1000527854 (X:68694746 C>G,T), RS1000566464 (X:68692759 T>C)

Disease associations

OMIM: gene MIM:300689 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST006661_233	Male-pattern baldness	5.000000e-61
GCST90002395_639	Mean platelet volume	2.000000e-53
GCST90002401_289	Platelet distribution width	2.000000e-31
GCST90002402_514	Platelet count	5.000000e-29

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007984	platelet component distribution width
EFO:0004309	platelet count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression	2
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	2
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
kojic acid	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
abrine	decreases expression	1
bisphenol S	increases expression	1
Temozolomide	decreases expression	1
Decitabine	affects expression	1
Sunitinib	decreases expression	1
Zoledronic Acid	decreases expression	1
Arbutin	decreases expression	1
Cisplatin	affects expression	1
Methapyrilene	increases methylation	1
Tamoxifen	affects expression	1
Valproic Acid	affects expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	decreases methylation	1
Antirheumatic Agents	decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.