GeneBe

SLC12A2

protein-coding

solute carrier family 12 member 2, the group of Solute carrier family 12|Protein phosphatase 1 regulatory subunits

Gene summary

The protein encoded by this gene mediates sodium and chloride transport and reabsorption. The encoded protein is a membrane protein and is important in maintaining proper ionic balance and cell volume. This protein is phosphorylated in response to DNA damage. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

MANE transcript

NM_001046.3

Inheritance

AD, AR

ClinVar variants

P:41U:389B:142

Top phenotype

Deafness, autosomal dominant 78; Delpire-McNeill syndrome; Kilquist syndrome

gnomAD constraint

pLI —, LoF o/e 0.19

Max pathogenic AF

—

Genomic locus

chr5:128,083,766-128,189,677

External References & Databases

Ensembl (ENSG00000064651)NCBI Gene (6558)OMIM (600840)HGNC:10911GenCCUniProt (P55011)AlphaFoldClinVar (SLC12A2)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~105.9 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Delpire-McNeill syndromeSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0033667

Submitter: Labcorp Genetics (formerly Invitae)

schizophreniaNO_KNOWN

Inheritance Pattern: Unknown

Disease ID:MONDO:0005090

Submitter: Labcorp Genetics (formerly Invitae)

hearing loss, autosomal dominant 78STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0033665

Submitter: Labcorp Genetics (formerly Invitae)

Kilquist syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0033664

Submitter: PanelApp Australia

Kilquist syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0033664

Submitter: Labcorp Genetics (formerly Invitae)

Delpire-McNeill syndromeSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0033667

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Deafness, autosomal dominant 78; Delpire-McNeill syndrome; Kilquist syndromeAD/AR

Manifestation: Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Craniofacial; Dermatologic; Gastrointestinal; Musculoskeletal; Neurologic; Pulmonary

Intervention: Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Pulmonary

Rationale: The conditions can include early-onset hearing loss, and early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; In Kilquist syndrome, antiinfectious prophylaxis and early and aggressive treatment of infections, as well as aggressive pulmonary care, may be beneficial

Refs: 30740830; 32658972; 32754646Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SLC12A2 variants in ClinVar

15 Conditions Cataloged
not providedTotal: 508
Inborn genetic diseasesTotal: 145
Delpire-McNeill syndromeTotal: 73
SLC12A2-related disorderTotal: 71
Kilquist syndromeTotal: 56
Hearing loss, autosomal dominant 78Total: 54
not specifiedTotal: 27
Hearing lossTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001046.3. 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.

EffectPLPVUSLBBSum
synonymous
3
clinvar
109
clinvar
5
clinvar
 117
missense
6
clinvar
2
clinvar
365
clinvar
27
clinvar
1
clinvar
 401
nonsense
6
clinvar
9
clinvar
4
clinvar
 19
start loss
0
frameshift
3
clinvar
5
clinvar
4
clinvar
 12
splice donor/acceptor (+/-2bp)
4
clinvar
6
clinvar
13
clinvar
 23
Total19223891366572

Highest pathogenic variant AF is 0.00001244185

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 19 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_001046.3RefSeqNP_001037.127MANE Select
ENST00000262461.7EnsemblENSP00000262461.227MANE Select
NM_001256461.2RefSeqNP_001243390.126Standard
ENST00000343225.4EnsemblENSP00000340878.426Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
slc12a2Danio rerio

Structure: melanocyte

Quality: area

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Vibrio cholerae infection - Homo sapiens (human)
  • Salivary secretion - Homo sapiens (human)
  • Pancreatic secretion - Homo sapiens (human)
  • miR-targeted genes in epithelium - TarBase
  • miR-targeted genes in lymphocytes - TarBase

Biological Process

  • ion transport
  • cell volume homeostasis
  • hyperosmotic response
  • gamma-aminobutyric acid signaling pathway
  • aging

Molecular Function

  • protein binding
  • sodium:potassium:chloride symporter activity
  • ammonium transmembrane transporter activity
  • sodium ion transmembrane transporter activity
  • sodium:chloride symporter activity

Cellular Component

  • plasma membrane
  • integral component of plasma membrane
  • membrane
  • apical plasma membrane
  • extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000262461
Coding exons
27
Length
105923
Individuals with no LoFs
125714
Homozygous LoFs
0
Heterozygous LoFs
20
Defined
125734
p
0.0000795
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense2.404305940.7230.00002937818
Missense (PolyPhen)135259.890.519453207
Synonymous-0.4732222131.040.00001072407
Loss of Function5.771158.70.1880.00000309736

Population LoF Frequency

PopulationCAFp-valueStatus
African0.0000620.000062rare
Latino/Admixed American0.0000640.000058rare
Ashkenazi Jewish0.000100.000099rare
East Asian0.0000550.000054rare
Finnish00.0absent
European (Non-Finnish)0.000120.00011rare
South Asian0.0000350.000033rare
Other0.000160.00016rare

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Electrically silent transporter system. Mediates sodium and chloride reabsorption. Plays a vital role in the regulation of ionic balance and cell volume.;

Recessive Scores

pRec
0.315

Intolerance Scores

LoFtool
0.0758
RVIS EVS
-1.31
RVIS percentile EVS
4.88

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.757

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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