STRA6

signaling receptor and transporter of retinol STRA6

Basic information

Region (hg38): 15:74179465-74212267

Links

ENSG00000137868 ∙ NCBI:64220 ∙ OMIM:610745 ∙ HGNC:30650 ∙ Uniprot:Q9BX79 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Matthew-Wood syndrome (Definitive), mode of inheritance: AR
• Matthew-Wood syndrome (Strong), mode of inheritance: AR
• Matthew-Wood syndrome (Strong), mode of inheritance: AR
• Matthew-Wood syndrome (Supportive), mode of inheritance: AD
• microphthalmia, isolated, with coloboma (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Microphthalmia, syndromic 9	AR	Cardiovascular	The condition can involve congenital cardiac anomalies, and awareness may allow early management	Cardiovascular; Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic; Pulmonary; Renal	11857549; 17503335; 17236193; 17273977; 19112531; 19213032; 19309693; 21901792; 22283518; 22686418

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the STRA6 gene.

• Matthew-Wood syndrome (132 variants)
• not provided (108 variants)
• Inborn genetic diseases (19 variants)
• Syndromic Microphthalmia, Recessive (6 variants)
• not specified (5 variants)
• STRA6-related condition (3 variants)
• Anophthalmia-microphthalmia syndrome (3 variants)
• STRA6-Related Disorder (1 variants)
• Microphthalmia, isolated, with coloboma 8 (1 variants)
• Microphthalmia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the STRA6 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			8	23	3	34
missense	5	2	51	5	7	70
nonsense	2	1				3
start loss						0
frameshift	7	2				9
inframe indel						0
splice donor/acceptor (+/-2bp)	1	2				3
splice region	1		5	3		9
non coding		1	26	23	44	94
Total	15	8	85	51	54

Highest pathogenic variant AF is 0.0000328

Variants in STRA6

This is a list of pathogenic ClinVar variants found in the STRA6 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
15-74179498-A-G		Matthew-Wood syndrome	Uncertain significance (Jan 13, 2018)
15-74179511-A-G		Matthew-Wood syndrome	Benign (Jan 13, 2018)
15-74179591-A-G		Matthew-Wood syndrome	Benign (Jan 12, 2018)
15-74179654-C-T		Syndromic Microphthalmia, Recessive	Uncertain significance (Jun 14, 2016)
15-74179681-C-T		Matthew-Wood syndrome	Uncertain significance (Jan 12, 2018)
15-74179699-G-A		Matthew-Wood syndrome	Uncertain significance (Jan 13, 2018)
15-74179712-C-G		Matthew-Wood syndrome	Uncertain significance (Jan 13, 2018)
15-74179756-G-A		Matthew-Wood syndrome	Uncertain significance (Jan 12, 2018)
15-74179858-C-T		Matthew-Wood syndrome	Benign (Jun 19, 2018)
15-74179871-C-G		Syndromic Microphthalmia, Recessive	Uncertain significance (Jun 14, 2016)
15-74179890-G-A		Matthew-Wood syndrome	Uncertain significance (Jan 13, 2018)
15-74179891-C-A		Matthew-Wood syndrome	Uncertain significance (Jan 13, 2018)
15-74179902-G-A		Matthew-Wood syndrome	Uncertain significance (Jan 12, 2018)
15-74179939-C-T		Matthew-Wood syndrome	Uncertain significance (Jan 12, 2018)
15-74179953-A-G		Matthew-Wood syndrome	Benign (Aug 14, 2018)
15-74179975-C-T		Matthew-Wood syndrome	Uncertain significance (Jan 13, 2018)
15-74179991-A-G		Matthew-Wood syndrome	Uncertain significance (Jan 12, 2018)
15-74180005-G-T		Matthew-Wood syndrome	Benign/Likely benign (Dec 23, 2018)
15-74180008-G-A		Matthew-Wood syndrome	Uncertain significance (Apr 27, 2017)
15-74180048-C-A		Matthew-Wood syndrome	Uncertain significance (Jan 12, 2018)
15-74180070-T-G		Matthew-Wood syndrome • STRA6-related disorder	Conflicting classifications of pathogenicity (Mar 02, 2020)
15-74180083-G-A		Matthew-Wood syndrome	Likely benign (Apr 24, 2019)
15-74180092-A-G		Matthew-Wood syndrome	Uncertain significance (Jan 12, 2018)
15-74180114-G-A		Matthew-Wood syndrome	Uncertain significance (Apr 20, 2022)
15-74180120-C-T		Matthew-Wood syndrome • STRA6-related disorder	Likely pathogenic (Dec 08, 2015)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
STRA6	protein_coding	protein_coding	ENST00000563965	19	32802

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.51e-10	0.987	125697	0	51	125748	0.000203

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.599	355	388	0.914	0.0000228	4441
Missense in Polyphen		63	97.497	0.64617		1226
Synonymous	-1.19	191	171	1.12	0.0000105	1521
Loss of Function	2.42	22	38.1	0.577	0.00000191	424

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000387	0.000380
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.000291	0.000273
Middle Eastern	0.000109	0.000109
South Asian	0.000163	0.000163
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Functions as 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 (PubMed:9452451, PubMed:18316031, PubMed:22665496). Retinol uptake is enhanced by LRAT, an enzyme that converts retinol to all-trans retinyl esters, the storage forms of vitamin A (PubMed:18316031, PubMed:22665496). 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 (PubMed:21368206, PubMed:22665496). Important for the homeostasis of vitamin A and its derivatives, such as retinoic acid (PubMed:18316031). STRA6-mediated transport is particularly important in the eye, and under conditions of dietary vitamin A deficiency (Probable). Does not transport retinoic acid (PubMed:18316031). {ECO:0000269|PubMed:18316031, ECO:0000269|PubMed:21901792, ECO:0000269|PubMed:22665496, ECO:0000269|PubMed:9452451, ECO:0000305}.
• Disease: DISEASE: 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. {ECO:0000269|PubMed:17273977, ECO:0000269|PubMed:17503335, ECO:0000269|PubMed:21368206, ECO:0000269|PubMed:21901792}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=Mutations in STRA6 may be a cause of isolated colobomatous microphthalmia, a disorder of the eye characterized by an abnormally small ocular globe. {ECO:0000269|PubMed:21901792}.
• Pathway: Signaling by GPCR;Signal Transduction;The canonical retinoid cycle in rods (twilight vision);G alpha (i) signalling events;Visual phototransduction;GPCR downstream signalling (Consensus)

Recessive Scores

• pRec: 0.103

Intolerance Scores

• loftool: 0.0677
• rvis_EVS: 0.3
• rvis_percentile_EVS: 71.64

Haploinsufficiency Scores

• pHI: 0.178
• hipred: N
• hipred_score: 0.173

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.185

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Stra6
• Phenotype: pigmentation phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); skeleton phenotype; vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype; homeostasis/metabolism phenotype; craniofacial phenotype

Zebrafish Information Network

• Gene name: stra6
• Affected structure: nucleate erythrocyte
• Phenotype tag: abnormal
• Phenotype quality: position

Gene ontology

• Biological process: retinoid metabolic process;blood vessel development;kidney development;pulmonary valve morphogenesis;ventricular septum development;heart development;learning;feeding behavior;lung development;adrenal gland development;female genitalia development;retinol transport;vocal learning;camera-type eye development;ear development;nose morphogenesis;lung alveolus development;positive regulation of behavior;digestive tract morphogenesis;embryonic digestive tract development;developmental growth;smooth muscle tissue development;artery morphogenesis;cognition;neuromuscular process;head development;head morphogenesis;face morphogenesis;lung vasculature development;diaphragm development;embryonic camera-type eye formation;eyelid development in camera-type eye;uterus morphogenesis;alveolar primary septum development;pulmonary artery morphogenesis;paramesonephric duct development;vitamin A import;ductus arteriosus closure
• Cellular component: plasma membrane;integral component of plasma membrane;protein-containing complex
• Molecular function: retinal binding;retinol binding;retinol transmembrane transporter activity;signaling receptor activity