SLCO2A1

protein-coding

solute carrier organic anion transporter family member 2A1, the group of Solute carrier organic anion transporter family

Gene summary

This gene encodes a prostaglandin transporter that is a member of the 12-membrane-spanning superfamily of transporters. The encoded protein may be involved in mediating the uptake and clearance of prostaglandins in numerous tissues. [provided by RefSeq, Dec 2011]

Previous symbols:

SLC21A2
MATR1

MANE transcript

NM_005630.3

Inheritance

AD, AR

ClinVar variants

P:68U:141B:107

Top phenotype

Hypertrophic osteoarthropathy, primary, autosomal dominant; PHOAR2-enteropathy syndrome

gnomAD constraint

pLI —, LoF o/e 0.75

Max pathogenic AF

—

Genomic locus

chr3:133,932,701-134,052,184

External References & Databases

Ensembl (ENSG00000174640)

Transcript & Mutation Effects

hg38 • Region Span ~119.5 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

hypertrophic osteoarthropathy, primary, autosomal dominantSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0008172

Submitter: PanelApp Australia

inflammatory bowel diseaseSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0005265

Submitter: PanelApp Australia

hypertrophic osteoarthropathy, primary, autosomal recessive, 2DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0013756

Submitter: G2P

hypertrophic osteoarthropathy, primary, autosomal recessive, 2STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013756

Submitter: Labcorp Genetics (formerly Invitae)

hypertrophic osteoarthropathy, primary, autosomal dominantDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0008172

Submitter: Ambry Genetics

hypertrophic osteoarthropathy, primary, autosomal recessive, 2STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013756

Submitter: Genomics England PanelApp

hypertrophic osteoarthropathy, primary, autosomal recessive, 2DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0013756

Submitter: Ambry Genetics

chronic enteropathy associated with SLCO2A1 geneSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0018766

Submitter: Orphanet

pachydermoperiostosisSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009799

Submitter: Orphanet

hypertrophic osteoarthropathy, primary, autosomal recessive, 2STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013756

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Hypertrophic osteoarthropathy, primary, autosomal dominant; PHOAR2-enteropathy syndromeAD/AR

Manifestation: Dermatologic; Gastrointestinal; Musculoskeletal

Intervention: Musculoskeletal

Rationale: For both dominant and recessive forms, medical management (eg, with etoricoxib) has been shown to be clinically beneficial related to manifestations affecting multiple organ systems (eg, joint swelling, skin manifestations)

Comments: Heterozygotes may show mild manifestations

Refs: 16283874; 20889364; 22553128; 22331663; 22197487; 28425581; 33852188

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SLCO2A1 variants in ClinVar

7 Conditions Cataloged

not providedTotal: 257

Inborn genetic diseasesTotal: 74

Hypertrophic osteoarthropathy, primary, autosomal recessive, 2Total: 67

SLCO2A1-related disorderTotal: 29

not specifiedTotal: 22

Hypertrophic osteoarthropathy, primary, autosomal dominantTotal: 14

Pachydermoperiostosis syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005630.3. 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			4 clinvar	76 clinvar	7 clinvar	87
missense	10 clinvar	12 clinvar	132 clinvar	22 clinvar	2 clinvar	178
nonsense	8 clinvar	8 clinvar	1 clinvar			17
start loss						0
frameshift	11 clinvar	7 clinvar				18
splice donor/acceptor (+/-2bp)	7 clinvar	5 clinvar	4 clinvar			16
Total	36	32	141	98	9	316

Highest pathogenic variant AF is 0.000077012795

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 29 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005630.3	RefSeq	NP_005621.2	14	MANE Select
ENST00000310926.11	Ensembl	ENSP00000311291.4	14	MANE Select
ENST00000481359.3	Ensembl	ENSP00000420028.3	9	Standard
ENST00000493729.5	Ensembl	ENSP00000418893.1	13	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Transport of vitamins, nucleosides, and related molecules
SLC-mediated transmembrane transport
Transport of small molecules
Prostaglandin formation from arachidonate
Transport of organic anions

Biological Process

lipid transport
prostaglandin transport
sodium-independent organic anion transport
transmembrane transport

Molecular Function

lipid transporter activity
prostaglandin transmembrane transporter activity
sodium-independent organic anion transmembrane transporter activity

Cellular Component

plasma membrane
integral component of plasma membrane
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000310926
Coding exons: 14
Length: 119489
Individuals with no LoFs: 125675
Homozygous LoFs: 0
Heterozygous LoFs: 73
Defined: 125748
p: 0.000290

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.518	339	367	0.924	0.0000202	4138
Missense (PolyPhen)		147	164.69	0.89257		1884
Synonymous	1.08	136	153	0.889	0.00000886	1322
Loss of Function	1.32	24	32.1	0.749	0.00000177	339

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0012	0.0012	notable
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00098	0.00098	rare
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.00020	0.00020	rare
South Asian	0.00017	0.00016	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May mediate the release of newly synthesized prostaglandins from cells, the transepithelial transport of prostaglandins, and the clearance of prostaglandins from the circulation. Transports PGD2, as well as PGE1, PGE2 and PGF2A.;

Recessive Scores

pRec: 0.176

Intolerance Scores

LoFtool: 0.891
RVIS EVS: 0.27
RVIS percentile EVS: 70.69

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.181

Gene Damage Prediction

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