STRA6

Summary

STRA6 (signaling receptor and transporter of retinol STRA6, HGNC:30650) is a protein-coding gene on chromosome 15q24.1, encoding Receptor for retinol uptake STRA6 (Q9BX79). Functions as a retinol transporter.

The protein encoded by this gene is a membrane protein involved in the metabolism of retinol. The encoded protein acts as a receptor for retinol/retinol binding protein complexes. This protein removes the retinol from the complex and transports it across the cell membrane. Defects in this gene are a cause of syndromic microphthalmia type 9 (MCOPS9). Several transcript variants encoding a few different isoforms have been found for this gene.

Source: NCBI Gene 64220 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Matthew-Wood syndrome (Definitive, GenCC) — +1 more curated relationship
• GWAS associations: 4
• Clinical variants (ClinVar): 332 total — 21 pathogenic, 10 likely-pathogenic
• Phenotypes (HPO): 57
• Druggable target: yes
• MANE Select transcript: NM_022369

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30650
Approved symbol	STRA6
Name	signaling receptor and transporter of retinol STRA6
Location	15q24.1
Locus type	gene with protein product
Status	Approved
Aliases	SLC69A1, FLJ12541
Ensembl gene	ENSG00000137868
Ensembl biotype	protein_coding
OMIM	610745
Entrez	64220

Gene structure

Transcript identifiers

Ensembl transcripts: 34 — 24 protein_coding, 5 retained_intron, 3 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000323940, ENST00000395105, ENST00000416286, ENST00000423167, ENST00000432245, ENST00000449139, ENST00000535552, ENST00000545137, ENST00000563965, ENST00000569936, ENST00000571341, ENST00000572785, ENST00000572975, ENST00000573214, ENST00000573391, ENST00000573456, ENST00000573724, ENST00000574278, ENST00000574439, ENST00000574570, ENST00000575272, ENST00000616000, ENST00000863855, ENST00000863856, ENST00000863857, ENST00000863858, ENST00000863859, ENST00000935164, ENST00000935165, ENST00000935166, ENST00000935167, ENST00000935168, ENST00000935169, ENST00000948078

RefSeq mRNA: 8 — MANE Select: NM_022369 NM_001142617, NM_001142618, NM_001142619, NM_001142620, NM_001199040, NM_001199041, NM_001199042, NM_022369

CCDS: CCDS10261, CCDS45301, CCDS45302, CCDS55973, CCDS55974, CCDS58387

Canonical transcript exons

ENST00000395105 — 19 exons

Exon	Start	End
ENSE00001520626	74202713	74202787
ENSE00001941786	74179466	74180243
ENSE00003461206	74180782	74180937
ENSE00003477645	74191167	74191243
ENSE00003482623	74190840	74190901
ENSE00003503917	74182161	74182262
ENSE00003509016	74191424	74191491
ENSE00003511085	74197752	74197818
ENSE00003540275	74189115	74189277
ENSE00003574892	74182343	74182460
ENSE00003588691	74195652	74195675
ENSE00003620902	74195302	74195468
ENSE00003634641	74184980	74185055
ENSE00003666436	74202155	74202282
ENSE00003681407	74181295	74181458
ENSE00003684967	74183856	74183989
ENSE00003691109	74193800	74193922
ENSE00003693432	74196008	74196147
ENSE00003788627	74197338	74197423

Expression profiles

Bgee: expression breadth ubiquitous, 128 present calls, max score 95.50.

FANTOM5 (CAGE): breadth broad, TPM avg 5.0064 / max 259.8616, expressed in 558 samples.

FANTOM5 promoters (13 alternative TSS)

Promoter ID	TPM avg	Samples expressed
150887	2.0657	372
150883	1.0217	322
150884	0.7812	280
150889	0.3054	163
150891	0.2465	87
150885	0.1636	95
150888	0.1469	60
150892	0.1251	71
150890	0.0981	43
150882	0.0194	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	95.50	gold quality
endometrium	UBERON:0001295	92.76	gold quality
placenta	UBERON:0001987	90.56	gold quality
endocervix	UBERON:0000458	89.58	gold quality
pituitary gland	UBERON:0000007	84.35	gold quality
adenohypophysis	UBERON:0002196	83.91	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.40	gold quality
right uterine tube	UBERON:0001302	83.02	gold quality
uterine cervix	UBERON:0000002	81.53	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	80.55	gold quality
right testis	UBERON:0004534	78.95	gold quality
prostate gland	UBERON:0002367	78.84	gold quality
fallopian tube	UBERON:0003889	78.34	gold quality
ectocervix	UBERON:0012249	77.63	gold quality
adult mammalian kidney	UBERON:0000082	76.81	gold quality
left testis	UBERON:0004533	76.76	gold quality
testis	UBERON:0000473	76.61	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.53	gold quality
vagina	UBERON:0000996	73.49	gold quality
lymph node	UBERON:0000029	73.30	gold quality
kidney	UBERON:0002113	73.17	gold quality
ganglionic eminence	UBERON:0004023	72.82	gold quality
left uterine tube	UBERON:0001303	70.43	gold quality
body of uterus	UBERON:0009853	69.76	gold quality
esophagus mucosa	UBERON:0002469	68.57	gold quality
metanephros cortex	UBERON:0010533	68.44	gold quality
gall bladder	UBERON:0002110	68.04	gold quality
lower esophagus mucosa	UBERON:0035834	67.96	gold quality
myometrium	UBERON:0001296	67.94	gold quality
adrenal tissue	UBERON:0018303	67.76	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): PGR, RARG

miRNA regulators (miRDB)

46 targeting STRA6, 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-4510	100.00	66.60	2050
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-4648	99.91	67.00	710
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-2116-3P	99.74	64.32	889
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-6762-3P	99.66	66.94	1188
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-520A-5P	99.35	66.72	1632
HSA-MIR-525-5P	99.35	66.85	1615
HSA-MIR-3692-5P	99.29	67.04	1421
HSA-MIR-3064-5P	99.26	66.13	1497
HSA-MIR-3085-3P	99.26	66.16	1490
HSA-MIR-6504-5P	99.26	65.95	1487

Literature-anchored findings (GeneRIF, showing 32)

• Mutations in STRA6 cause a broad spectrum of malformations including anophthalmia, congenital heart defects, diaphragmatic hernia, alveolar capillary dysplasia, lung hypoplasia, and mental retardation (PMID:17273977)
• Matthew-Wood syndrome is caused by truncating mutations in the retinol-binding protein receptor gene STRA6. (PMID:17503335)
• In fibroboasts, STRA6 transports retinol bidirectionally in an RBP4 dependent manner. (PMID:18316031)
• study identifies an essential functional domain in STRA6 and a human polymorphism in this domain that leads to reduced vitamin A uptake activity (PMID:18387951)
• This study explores the association of STRA6 and SKI genes in a cohort of subjects with anophthalmia and microphthalmia. (PMID:19112531)
• Two novel STRA6 mutations in a patient with anophthalamia and diaphragmatic eventration are reported. (PMID:19213032)
• Six novel mutations were identified in STRA6. (PMID:19309693)
• SNPs in STRA6, gene coding the cell surface receptor for RBP4, were significantly associated with type 2 diabetes and further genetic and functional studies are required to understand and ascertain its role in the manifestation of type 2 diabetes. (PMID:20625434)
• STRA6 mutations can cause isolated eye malformations in addition to the congenital anomalies observed in MWS. (PMID:21901792)
• Analysis of FRAS1 and STRA6 mutations in the same family with eye anomalies. (PMID:22283518)
• STRA6 orchestrates a multicomponent machinery that couples vitamin A homeostasis and metabolism to activation of a signaling cascade and that, in turn, STRA6 signaling regulates the cellular uptake of the vitamin. (PMID:22665496)
• Findings suggest that heterozygosity for the STRA6 gene mutation may be associated with ocular abnormalities. (PMID:22686418)
• TTR blocks the ability of holo-retinol-binding protein to associate with STRA6 and thereby effectively suppresses both STRA6-mediated retinol uptake and STRA6-initiated cell signaling. (PMID:22826435)
• Stra6, a retinoic acid-responsive gene, participates in p53-induced apoptosis after DNA damage. (PMID:23449393)
• Evidence for the existence of a transmembrane pore, analogous to the pore of ion channels, in STRA6. (PMID:24223695)
• STRA6 has a role for regulating retinoid homeostasis and in helping to program signaling that drives proliferation and differentiation of human skin cells (PMID:24284421)
• These data establish that holo-RBP and its receptor STRA6 are potent oncogenes and suggest that the pathway is a novel target for therapy of some human cancers. (PMID:25237067)
• A novel mutation in two Hmong families broadens the range of STRA6-related malformations to include contractures and camptodactyly. (PMID:26373900)
• this study suggested that a role of STRA6 polymorphism could also be of value in predicting the risk of type 2 diabetes mellitus(T2DM) while RARRES2 polymorphism could not predict the risk of T2DM (PMID:27446956)
• these data demonstrate a key role of STRA6 and RBP4 in the maintenance of colon cancer self-renewal and that this pathway is an important link through which consumption of HFD contributes to colon carcinogenesis. (PMID:28689994)
• The knockdown of STRA6 slightly enhanced nodule formation at the late stage of osteoblast differentiation, and overexpression of STRA6 in ST2 cells enhanced adipocyte differentiation. (PMID:29067460)
• We demonstrate that mutations in STRA6 are the cause for syndromic anophthalmia in the original Matthew-Wood patient (PMID:29168296)
• Mutations in retinoic acid 6 gene (STRA6) have been reported in clinically diagnosed patients with MWS. Here we presented a case with MWS, who has characteristic findings of the syndrome as well as dextrocardia as an undescribed feature, and bilateral streak gonads which was described only in one patient previously. Molecular analysis showed a homozygous exonic missense mutation in the STRA6 gene. (PMID:30204971)
• SRC-2 is required for full induction of the retinol transporter, stimulated by retinoic acid 6 (STRA6), which is essential for endometrial stromal cell decidualization. (PMID:30325183)
• significant association between STRA6 polymorphism and Gestational diabetes mellitus in Chinese Han population (PMID:30882700)
• The protective variant rs7173049 at LOXL1 locus impacts on retinoic acid signaling pathway in pseudoexfoliation syndrome. (PMID:30986821)
• Electronegative low-density lipoprotein of patients with metabolic syndrome induces pathogenesis of aorta through disruption of the stimulated by retinoic acid 6 cascade. (PMID:31597015)
• STRA6 is down-regulated by miR-873 and plays an oncogenic role by activating Wnt/beta-catenin signalling in GC. (PMID:31694721)
• STRA6 Expression Serves as a Prognostic Biomarker of Gastric Cancer. (PMID:32859629)
• STRA6 is essential for induction of vascular smooth muscle lineages in human embryonic cardiac outflow tract development. (PMID:36635482)
• Up-regulation of STRA6 predicts poor prognosis and contributes to oxaliplatin resistance in colorectal cancer. (PMID:36758416)
• STRA6 regulates tumor immune microenvironment and is a prognostic marker in BRAF-mutant papillary thyroid carcinoma. (PMID:36843593)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	stra6	ENSDARG00000051874
mus_musculus	Stra6	ENSMUSG00000032327
rattus_norvegicus	Stra6	ENSRNOG00000008312

Paralogs (1): CCDC180 (ENSG00000197816)

Protein

Protein identifiers

Receptor for retinol uptake STRA6 — Q9BX79 (reviewed: Q9BX79)

Alternative names: Retinol-binding protein receptor STRA6, Stimulated by retinoic acid gene 6 protein homolog

All UniProt accessions (6): Q9BX79, I3L0M6, I3L1C7, I3L2B6, I3NI08, J3KQI6

UniProt curated annotations — full annotation on UniProt →

Function. Functions as a retinol transporter. Accepts all-trans retinol from the extracellular retinol-binding protein RBP4, facilitates retinol transport across the cell membrane, and then transfers retinol to the cytoplasmic retinol-binding protein RBP1. Retinol uptake is enhanced by LRAT, an enzyme that converts retinol to all-trans retinyl esters, the storage forms of vitamin A. Contributes to the activation of a signaling cascade that depends on retinol transport and LRAT-dependent generation of retinol metabolites that then trigger activation of JAK2 and its target STAT5, and ultimately increase the expression of SOCS3 and inhibit cellular responses to insulin. Important for the homeostasis of vitamin A and its derivatives, such as retinoic acid. STRA6-mediated transport is particularly important in the eye, and under conditions of dietary vitamin A deficiency. Does not transport retinoic acid.

Subunit / interactions. Homodimer. Interacts with JAK2 and STAT5. Interacts (via extracellular domains) with RBP4. Interacts (via cytoplasmic domains) with RBP1.

Subcellular location. Cell membrane.

Tissue specificity. Broad expression. In adult eye expressed in sclera, retina, retinal pigment epithelium, and trabecular meshwork but not in choroid and iris.

Post-translational modifications. Phosphorylated on tyrosine residues in response to RBP4 binding. Phosphorylation requires the presence of LRAT, suggesting it may be triggered by the uptake of retinol that is then metabolized within the cell to retinoids that function as signaling molecules.

Disease relevance. Microphthalmia, syndromic, 9 (MCOPS9) [MIM:601186] A rare clinical entity including as main characteristics anophthalmia or severe microphthalmia, and pulmonary hypoplasia or aplasia. Microphthalmia is a disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues (anophthalmia). In many cases, microphthalmia/anophthalmia occurs in association with syndromes that include non-ocular abnormalities. The disease is caused by variants affecting the gene represented in this entry. Mutations in STRA6 may be a cause of isolated colobomatous microphthalmia, a disorder of the eye characterized by an abnormally small ocular globe.

Domain organisation. Contrary to predictions, contains nine transmembrane helices, with an extracellular N-terminus and a cytoplasmic C-terminus. Besides, contains one long helix that dips into the membrane and then runs more or less parallel to the membrane surface.

Induction. Up-regulated in the colorectal cancer cell line WiDr by the administration of retinoic acid and in tumors with frequent defects in Wnt-1 signaling.

Isoforms (6)

UniProt ID	Names	Canonical?
Q9BX79-1	1	yes
Q9BX79-2	2
Q9BX79-3	3
Q9BX79-4	4
Q9BX79-5	5
Q9BX79-6	6

RefSeq proteins (8): NP_001136089, NP_001136090, NP_001136091, NP_001136092, NP_001185969, NP_001185970, NP_001185971, NP_071764* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026612	STRA6-like	Family

Pfam: PF14752

UniProt features (50 total): sequence variant 12, topological domain 11, transmembrane region 9, splice variant 5, sequence conflict 4, region of interest 2, mutagenesis site 2, chain 1, intramembrane region 1, compositionally biased region 1, modified residue 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BX79-F1	78.18	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.

Post-translational modifications (1): 643

Glycosylation sites (1): 8

Mutagenesis-validated functional residues (2):

Position	Phenotype
255	loss of interaction with rbp1.
643	loss of tyrosine phosphorylation.

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-2453902	The canonical retinoid cycle in rods (twilight vision)
R-HSA-9918449	Defective visual phototransduction due to STRA6 loss of function
R-HSA-1643685	Disease
R-HSA-2187338	Visual phototransduction
R-HSA-2453864	Retinoid cycle disease events
R-HSA-2474795	Diseases associated with visual transduction
R-HSA-9675143	Diseases of the neuronal system
R-HSA-9709957	Sensory Perception

MSigDB gene sets: 0 (showing top):

GO Biological Process (37): blood vessel development (GO:0001568), kidney development (GO:0001822), pulmonary valve morphogenesis (GO:0003184), ventricular septum development (GO:0003281), heart development (GO:0007507), learning (GO:0007612), feeding behavior (GO:0007631), lung development (GO:0030324), adrenal gland development (GO:0030325), female genitalia development (GO:0030540), retinol transport (GO:0034633), vocal learning (GO:0042297), camera-type eye development (GO:0043010), ear development (GO:0043583), nose morphogenesis (GO:0043585), lung alveolus development (GO:0048286), positive regulation of behavior (GO:0048520), digestive tract morphogenesis (GO:0048546), embryonic digestive tract development (GO:0048566), developmental growth (GO:0048589), smooth muscle tissue development (GO:0048745), artery morphogenesis (GO:0048844), cognition (GO:0050890), neuromuscular process (GO:0050905), head development (GO:0060322), head morphogenesis (GO:0060323), face morphogenesis (GO:0060325), lung vasculature development (GO:0060426), diaphragm development (GO:0060539), embryonic camera-type eye formation (GO:0060900), eyelid development in camera-type eye (GO:0061029), uterus morphogenesis (GO:0061038), alveolar primary septum development (GO:0061143), pulmonary artery morphogenesis (GO:0061156), paramesonephric duct development (GO:0061205), vitamin A import into cell (GO:0071939), ductus arteriosus closure (GO:0097070)

GO Molecular Function (5): retinal binding (GO:0016918), retinol binding (GO:0019841), retinol transmembrane transporter activity (GO:0034632), signaling receptor activity (GO:0038023), protein binding (GO:0005515)

GO Cellular Component (3): plasma membrane (GO:0005886), protein-containing complex (GO:0032991), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Visual phototransduction	1
Retinoid cycle disease events	1
Sensory Perception	1
Diseases associated with visual transduction	1
Diseases of the neuronal system	1
Disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
animal organ development	3
anatomical structure development	2
behavior	2
digestive tract development	2
retinoid binding	2
vitamin binding	2
vasculature development	1
renal system development	1
pulmonary valve development	1
heart valve morphogenesis	1
cardiac ventricle development	1
cardiac septum development	1
circulatory system development	1
learning or memory	1
respiratory tube development	1
respiratory system development	1
endocrine system development	1
gland development	1
female sex differentiation	1
genitalia development	1
organic hydroxy compound transport	1
terpenoid transport	1
auditory behavior	1
imitative learning	1
learned vocalization behavior or vocal learning	1
eye development	1
sensory organ development	1
nose development	1
sensory organ morphogenesis	1
lung development	1
regulation of behavior	1
positive regulation of multicellular organismal process	1
tube morphogenesis	1
embryonic organ development	1
developmental process	1
growth	1
alcohol binding	1
alcohol transmembrane transporter activity	1
retinol transport	1
vitamin transmembrane transporter activity	1

Protein interactions and networks

STRING

1401 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
STRA6	RBP4	P02753	993
STRA6	RBP1	P09455	959
STRA6	LRAT	O95237	850
STRA6	RARA	P10276	761
STRA6	CYP26A1	O43174	733
STRA6	CALML6	Q8TD86	722
STRA6	CALML3	P27482	722
STRA6	CALML5	Q9NZT1	722
STRA6	CALML4	Q96GE6	722
STRA6	RDH10	Q8IZV5	695
STRA6	ALDH1A3	P47895	657
STRA6	CYP26B1	Q9NR63	648
STRA6	TTR	P02766	644
STRA6	RARS1	P54136	639
STRA6	CRABP1	P29762	620

IntAct

23 interactions, top by confidence:

A	B	Type	Score
TRDN	TMEM223	psi-mi:“MI:0914”(association)	0.640
ATP1A3	AGPAT2	psi-mi:“MI:0914”(association)	0.530
B4GAT1	ADCY6	psi-mi:“MI:0914”(association)	0.530
CMKLR1	SC5D	psi-mi:“MI:0914”(association)	0.530
GPRC5B	STXBP3	psi-mi:“MI:0914”(association)	0.530
LDLRAD1	ADAM10	psi-mi:“MI:0914”(association)	0.530
SLC30A2	ESYT2	psi-mi:“MI:0914”(association)	0.530
STRA6	JAK2	psi-mi:“MI:0915”(physical association)	0.400
	TMEM223	psi-mi:“MI:0914”(association)	0.350
STRA6	GPR89A	psi-mi:“MI:0914”(association)	0.350
ATF7IP2	SETDB1	psi-mi:“MI:0914”(association)	0.350
ACKR3	PDE2A	psi-mi:“MI:0914”(association)	0.350
CCR9	ABCC4	psi-mi:“MI:0914”(association)	0.350
CXCR3	RIMOC1	psi-mi:“MI:0914”(association)	0.350
CXCR4	ESYT2	psi-mi:“MI:0914”(association)	0.350
EDEM2	HIGD1C	psi-mi:“MI:0914”(association)	0.350
SAAL1	TMEM223	psi-mi:“MI:0914”(association)	0.350
SLC39A4	GPR39	psi-mi:“MI:0914”(association)	0.350
TMED10	TMED7-TICAM2	psi-mi:“MI:0914”(association)	0.350
TMEM154	SMCHD1	psi-mi:“MI:0914”(association)	0.350
TMEM169	PTGES3L-AARSD1	psi-mi:“MI:0914”(association)	0.350

BioGRID (24): STRA6 (Affinity Capture-MS), STRA6 (Two-hybrid), STRA6 (Two-hybrid), KRTAP10-6 (Two-hybrid), KRTAP6-3 (Two-hybrid), STRA6 (Affinity Capture-MS), STRA6 (Affinity Capture-MS), STRA6 (Proximity Label-MS), STRA6 (Proximity Label-MS), STRA6 (Proximity Label-MS), STRA6 (Proximity Label-MS), STRA6 (Negative Genetic), STRA6 (Affinity Capture-MS), STXBP3 (Affinity Capture-MS), PTPN1 (Affinity Capture-MS)

ESM2 similar proteins: A0A140LIJ0, A1L3G9, A4IFL1, B9X187, O18968, O70491, P08033, P08034, P28230, P35212, P36380, P51915, P60572, Q02738, Q059Y8, Q0V8E7, Q1LXZ7, Q28FG4, Q29559, Q4QR83, Q5E9Z5, Q5FVF4, Q5FWS4, Q5JW98, Q5R7B4, Q5T197, Q5T1A1, Q60HF7, Q640M6, Q6GMB1, Q6WGK6, Q7SY10, Q7TNJ0, Q8BXV2, Q8C2L6, Q8C9E8, Q8CE93, Q8CEG0, Q8N5C1, Q8NDZ6

Diamond homologs: F1RAX4, O70491, Q0V8E7, Q4QR83, Q5R7B4, Q9BX79

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
STRA6	“up-regulates quantity”	retinol	relocalization

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 36 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of cytosolic calcium ion concentration	6	22.6×	7e-05
immune response	6	9.1×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	21
Likely pathogenic	10
Uncertain significance	158
Likely benign	58
Benign	45

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1030805	NM_022369.4(STRA6):c.62dup (p.Ser22fs)	Pathogenic
1134	NM_022369.4(STRA6):c.147del (p.Gly50fs)	Pathogenic
1137	NM_022369.4(STRA6):c.269C>T (p.Pro90Leu)	Pathogenic
1139	NM_022369.4(STRA6):c.50_52delinsCC (p.Asp17fs)	Pathogenic
1141	NM_022369.4(STRA6):c.35_36dup (p.Gly13fs)	Pathogenic
1142	NM_022369.4(STRA6):c.69G>A (p.Trp23Ter)	Pathogenic
1334721	NM_022369.4(STRA6):c.1594C>T (p.Arg532Ter)	Pathogenic
1387638	NM_022369.4(STRA6):c.985del (p.Val329fs)	Pathogenic
194560	NM_022369.4(STRA6):c.1385del (p.Asn462fs)	Pathogenic
221927	NM_022369.4(STRA6):c.1735C>G (p.Pro579Ala)	Pathogenic
221966	NM_022369.4(STRA6):c.1313A>G (p.Gln438Arg)	Pathogenic
221967	NM_022369.4(STRA6):c.1913G>C (p.Arg638Pro)	Pathogenic
39742	NM_022369.4(STRA6):c.910_911delinsAA (p.Gly304Lys)	Pathogenic
40078	NM_022369.4(STRA6):c.1678G>C (p.Asp560His)	Pathogenic
418507	NM_022369.4(STRA6):c.582_583insTTGGCAGAGGGCAGAGTGT (p.Pro195fs)	Pathogenic
572841	NM_022369.4(STRA6):c.1676dup (p.Asp560fs)	Pathogenic
88764	NM_022369.4(STRA6):c.1521-1G>A	Pathogenic
915291	NM_022369.4(STRA6):c.438G>A (p.Trp146Ter)	Pathogenic
936558	NM_022369.4(STRA6):c.481del (p.Leu161fs)	Pathogenic
984924	NM_022369.4(STRA6):c.347del (p.Leu116fs)	Pathogenic
984925	NM_022369.4(STRA6):c.1301-6T>A	Pathogenic
1064531	NM_022369.4(STRA6):c.1285G>C (p.Ala429Pro)	Likely pathogenic
1133	NM_022369.4(STRA6):c.878C>T (p.Pro293Leu)	Likely pathogenic
1140	NM_022369.4(STRA6):c.527dup (p.Ser177fs)	Likely pathogenic
1328571	NM_022369.4(STRA6):c.1167-2_1167-1del	Likely pathogenic
1710342	NM_022369.4(STRA6):c.1699C>T (p.Arg567Ter)	Likely pathogenic
3780680	NM_022369.4(STRA6):c.92dup (p.Glu32fs)	Likely pathogenic
446174	NM_022369.4(STRA6):c.113+3_113+4del	Likely pathogenic
451461	NM_022369.4(STRA6):c.344_345del (p.Cys115fs)	Likely pathogenic
951027	NM_022369.4(STRA6):c.1418+1_1418+3del	Likely pathogenic

SpliceAI

3554 predictions. Top by Δscore:

Variant	Effect	Δscore
15:74180790:T:TA	donor_gain	1.0000
15:74181289:CCTTA:C	donor_loss	1.0000
15:74181290:CTTAC:C	donor_loss	1.0000
15:74181292:TAC:T	donor_loss	1.0000
15:74181410:C:CT	acceptor_gain	1.0000
15:74181411:A:T	acceptor_gain	1.0000
15:74181413:C:CT	acceptor_gain	1.0000
15:74181415:C:CT	acceptor_gain	1.0000
15:74181416:A:C	acceptor_gain	1.0000
15:74181417:T:C	acceptor_gain	1.0000
15:74181417:T:TC	acceptor_gain	1.0000
15:74181454:CTCGC:C	acceptor_gain	1.0000
15:74181456:CGC:C	acceptor_gain	1.0000
15:74181457:GCC:G	acceptor_loss	1.0000
15:74181458:CCT:C	acceptor_loss	1.0000
15:74181459:CT:C	acceptor_loss	1.0000
15:74181460:T:A	acceptor_loss	1.0000
15:74182339:T:TA	donor_loss	1.0000
15:74182341:A:AC	donor_gain	1.0000
15:74182342:C:CC	donor_gain	1.0000
15:74182342:CCA:C	donor_gain	1.0000
15:74182456:GAGCC:G	acceptor_gain	1.0000
15:74182457:AGCC:A	acceptor_gain	1.0000
15:74182458:GCC:G	acceptor_gain	1.0000
15:74182459:CC:C	acceptor_gain	1.0000
15:74182459:CCC:C	acceptor_gain	1.0000
15:74182460:CC:C	acceptor_gain	1.0000
15:74182461:C:CA	acceptor_loss	1.0000
15:74182461:C:CC	acceptor_gain	1.0000
15:74182462:T:C	acceptor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000136287 (15:74209706 A>G,T), RS1000323466 (15:74182523 C>T), RS1000412321 (15:74210416 A>C), RS1000556315 (15:74192414 G>A), RS1000994283 (15:74205541 C>T), RS1000994322 (15:74203948 G>A,C), RS1000999788 (15:74199863 G>A), RS1001052843 (15:74192695 C>A,T), RS1001075204 (15:74197954 C>A,G,T), RS1001156211 (15:74199488 G>A,C,T), RS1001248282 (15:74205856 G>A), RS1001320045 (15:74202376 C>G,T), RS1001351064 (15:74202643 C>A,G,T), RS1001377569 (15:74193642 G>A), RS1001420739 (15:74204133 A>G)

Disease associations

OMIM: gene MIM:610745 | disease phenotypes: MIM:601186

GenCC curated gene-disease

Disease	Classification	Inheritance
Matthew-Wood syndrome	Definitive	Autosomal recessive
microphthalmia, isolated, with coloboma	Supportive	Autosomal dominant

Mondo (4): Matthew-Wood syndrome (MONDO:0011010), microphthalmia (MONDO:0021129), microphthalmia, isolated, with coloboma 8 (MONDO:0800324), microphthalmia, isolated, with coloboma (MONDO:0000170)

Orphanet (2): Matthew-Wood syndrome (Orphanet:2470), Microphthalmia-anophthalmia-coloboma (Orphanet:98555)

HPO phenotypes

57 total (30 of 57 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000013	Hypoplasia of the uterus
HP:0000023	Inguinal hernia
HP:0000028	Cryptorchidism
HP:0000076	Vesicoureteral reflux
HP:0000085	Horseshoe kidney
HP:0000089	Renal hypoplasia
HP:0000125	Pelvic kidney
HP:0000126	Hydronephrosis
HP:0000130	Abnormality of the uterus
HP:0000347	Micrognathia
HP:0000369	Low-set ears
HP:0000431	Wide nasal bridge
HP:0000528	Anophthalmia
HP:0000568	Microphthalmia
HP:0000581	Blepharophimosis
HP:0000776	Congenital diaphragmatic hernia
HP:0000813	Bicornuate uterus
HP:0001249	Intellectual disability
HP:0001252	Hypotonia
HP:0001290	Generalized hypotonia
HP:0001508	Failure to thrive
HP:0001511	Intrauterine growth retardation
HP:0001629	Ventricular septal defect
HP:0001631	Atrial septal defect
HP:0001636	Tetralogy of Fallot
HP:0001642	Pulmonic stenosis
HP:0001643	Patent ductus arteriosus
HP:0001660	Truncus arteriosus
HP:0001680	Coarctation of aorta

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST005246_9	Inhibitory control	7.000000e-06
GCST008058_291	Estimated glomerular filtration rate	2.000000e-11
GCST009462_82	Optic disc size	1.000000e-08
GCST010108_18	Coffee consumption (cups per day)	1.000000e-19

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0008467	behavioural inhibitory control measurement
EFO:0006782	cups of coffee per day measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D008850	Microphthalmos	C11.250.566; C16.131.384.666
C537768	Anophthalmia with pulmonary hypoplasia (supp.)
C537463	Microphthalmia associated with colobomatous cyst (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067365 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.40	Kd	39.41	nM	CHEMBL3752910
7.13	ED50	73.54	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149946: Binding affinity to human STRA6 incubated for 45 mins by Kinobead based pull down assay	kd	0.0394	uM

CTD chemical–gene interactions

48 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	4
Valproic Acid	increases expression, affects cotreatment	4
trichostatin A	affects cotreatment, increases expression	3
Tobacco Smoke Pollution	affects expression, decreases expression, increases expression	3
Tretinoin	affects cotreatment, increases expression	3
entinostat	increases expression, affects cotreatment	2
(+)-JQ1 compound	decreases expression	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Aflatoxin B1	increases methylation	2
Cadmium Chloride	decreases expression, increases abundance	2
methylmercuric chloride	decreases expression	1
bisphenol A	affects cotreatment, increases expression	1
2,5,2’,5’-tetrachlorobiphenyl	decreases expression	1
beta-lapachone	decreases expression	1
arsenite	decreases methylation	1
cupric chloride	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases expression, affects response to substance, increases expression	1
diallyl trisulfide	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	increases expression	1
dorsomorphin	increases expression, affects cotreatment	1
jinfukang	affects cotreatment, increases expression	1
3-hydroxy-4-prenyl-5-methoxystilbene-2-carboxylic acid	increases expression	1
Temozolomide	increases expression	1
Arsenic Trioxide	decreases expression	1
Air Pollutants	decreases expression	1
Vehicle Emissions	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation, decreases methylation	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652988	Binding	Binding affinity to human STRA6 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D8BU	Ubigene A-549 STRA6 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01778543	Not specified	RECRUITING	Pathogenesis and Genetics of Microphthalmia, Anophthalmia and Uveal Coloboma (MAC)
NCT03748732	Not specified	UNKNOWN	Extensive Circumferential Partial Thickness Sclerectomy in Nanophthalmic Eyes
NCT04759560	Not specified	UNKNOWN	Biometric Characteristics of the Eye With Microcornea/Microphthalmia and Congenital Cataract Before And After Cataract Extraction
NCT05954403	Not specified	RECRUITING	National Cohort on Congenital Defects of the Eye
NCT06293560	Not specified	RECRUITING	Microphthalmia, Anophthalmia, and Coloboma Genetic Epidemiology in Children