SLC9A9

Chr 3

solute carrier family 9 member A9

Also known as: AUTS16, NHE9

NCBI Gene: 285195 ENSG00000181804 UniProt: Q8IVB4

This gene encodes a sodium/proton exchanger that is a member of the solute carrier 9 protein family. The encoded protein localizes the to the late recycling endosomes and may play an important role in maintaining cation homeostasis. Mutations in this gene are associated with autism susceptibility 16 and attention-deficit/hyperactivity disorder. [provided by RefSeq, Mar 2012]

Research

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtAutism 16

Clinical highlights

Gene–disease validity (ClinGen)

Disputed · autism spectrum disorder · AD · ClinGen 2020

evidence questions this relationship

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.95

LOEUF

LOF*

Mechanism· G2P

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.95LOEUF

pLI 0.000

Z-score 1.77

OE 0.67 (0.48–0.95)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.25Z-score

OE missense 1.04 (0.95–1.13)

360 obs / 347.0 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.67 (0.48–0.95)

0≤0.351.4

Missense OE?1.04 (0.95–1.13)

0≤0.61.4

Synonymous OE?1.15

0≤1.21.6

LoF obs/exp: 23 / 34.1Missense obs/exp: 360 / 347.0Syn Z: -1.39

Background carrier burden — how many people carry a rare variant somewhere in SLC9A9?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 78

828 rare PASS variants

Rare truncating (LoF)

1 in 1,200

122 rare PASS variants

Rare synonymous (reference)

1 in 77

336 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SLC9A9. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 120	1 in 2,000
South Asian	~43k	1 in 66	1 in 1,300
Remaining (unassigned)	~30k	1 in 74	1 in 500
European (Finnish)	~27k	1 in 280	≈ 1 in 6,700
Admixed American	~22k	1 in 83	1 in 1,400
African / African American	~21k	1 in 60	1 in 1,700
East Asian	~20k	1 in 89	1 in 540
Ashkenazi Jewish	~13k	1 in 170	1 in 240
Middle Eastern	~2,884	1 in 54	≈ 1 in 960

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 16 coding exons well covered in gnomAD exomes and genomes.? see exons ↓