SLC9A7

protein-coding

solute carrier family 9 member A7, the group of Solute carrier family 9

Gene summary

This gene encodes a sodium and potassium/ proton antiporter that is a member of the solute carrier family 9 protein family. The encoded protein is primarily localized to the trans-Golgi network and is involved in maintaining pH homeostasis in organelles along the secretory and endocytic pathways. This protein may enhance cell growth of certain breast tumors. This gene is part of a gene cluster on chromosome Xp11.23. A pseudogene of this gene is found on chromosome 12. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Mar 2012]

MANE transcript

NM_001257291.2

Inheritance

ClinVar variants

P:2U:215B:58

Top phenotype

Intellectual developmental disorder, X-linked 108

gnomAD constraint

pLI —, LoF o/e 0.08

Max pathogenic AF

—

Genomic locus

chrX:46,599,251-46,759,118

External References & Databases

Ensembl (ENSG00000065923)

Transcript & Mutation Effects

hg38 • Region Span ~159.9 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

non-syndromic X-linked intellectual disabilitySUPPORTIVE

Inheritance Pattern: XL

Disease ID:MONDO:0019181

Submitter: Orphanet

intellectual developmental disorder, X-linked 108STRONG

Inheritance Pattern: XL

Disease ID:MONDO:0026723

Submitter: Labcorp Genetics (formerly Invitae)

intellectual developmental disorder, X-linked 108MODERATE

Inheritance Pattern: XL

Disease ID:MONDO:0026723

Submitter: PanelApp Australia

intellectual developmental disorder, X-linked 108LIMITED

Inheritance Pattern: XL

Disease ID:MONDO:0026723

Submitter: G2P

intellectual developmental disorder, X-linked 108LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0026723

Submitter: Labcorp Genetics (formerly Invitae)

intellectual developmental disorder, X-linked 108LIMITED

Inheritance Pattern: XL

Disease ID:MONDO:0026723

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Intellectual developmental disorder, X-linked 108XL

Manifestation: Craniofacial; Musculoskeletal; Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 30335141

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SLC9A7 variants in ClinVar

6 Conditions Cataloged

not providedTotal: 175

not specifiedTotal: 82

Intellectual developmental disorder, X-linked 108Total: 21

SLC9A7-related disorderTotal: 4

SLC9A7-related neurodevelopmental disorderTotal: 1

See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001257291.2. 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			14 clinvar	36 clinvar	6 clinvar	56
missense		1 clinvar	178 clinvar	14 clinvar	2 clinvar	195
nonsense			7 clinvar			7
start loss						0
frameshift			4 clinvar			4
splice donor/acceptor (+/-2bp)		1 clinvar	12 clinvar			13
Total	0	2	215	50	8	275

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 16 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001257291.2	RefSeq	NP_001244220.1	17	MANE Select
ENST00000616978.5	Ensembl	ENSP00000480916.1	17	MANE Select
NM_032591.3	RefSeq	NP_115980.1	17	Standard
ENST00000328306.4	Ensembl	ENSP00000330320.4	17	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Sodium/Proton exchangers
Transport of inorganic cations/anions and amino acids/oligopeptides
SLC-mediated transmembrane transport
Transport of small molecules

Biological Process

ion transport
regulation of pH
regulation of intracellular pH
potassium ion transmembrane transport
sodium ion import across plasma membrane

Molecular Function

protein binding
sodium:proton antiporter activity
potassium:proton antiporter activity
protein homodimerization activity

Cellular Component

Golgi membrane
trans-Golgi network
plasma membrane
integral component of membrane
intracellular membrane-bounded organelle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000328306
Coding exons: 17
Length: 153738
Individuals with no LoFs: 125733
Homozygous LoFs: 3
Heterozygous LoFs: 9
Defined: 125745
p: 0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.12	177	276	0.641	0.0000220	4716
Missense (PolyPhen)		35	71.09	0.49234		1291
Synonymous	0.179	117	119	0.979	0.0000106	1462
Loss of Function	4.14	2	23.8	0.0839	0.00000177	406

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.00014	0.000099	rare
East Asian	0.00030	0.00022	rare
Finnish	0.000063	0.000046	rare
European (Non-Finnish)	0.000062	0.000044	rare
South Asian	0.000054	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Mediates electroneutral exchange of protons for Na(+) and K(+) across endomembranes. May contribute to Golgi volume and cation homeostasis. {ECO:0000269|PubMed:11279194}.;

Recessive Scores

pRec: 0.141

Intolerance Scores

LoFtool: 0.270
RVIS EVS: -0.56
RVIS percentile EVS: 19.54

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.367

Gene Damage Prediction

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