SLC9A9

Chr 3

solute carrier family 9 member A9

Also known as: AUTS16, NHE9

NCBI Gene: 285195 ENSG00000181804 UniProt: Q8IVB4 OMIM: 608396

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]

OMIM Research

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.951 OMIM phenotype

Clinical Summary— SLC9A9

🧬

Gene-Disease Validity (ClinGen)

autism spectrum disorder · ADDisputed

Disputed — evidence questions this relationship

⚡

Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

📋

ClinVar Variants

2 unique Pathogenic / Likely Pathogenic· 93 VUS of 146 total submissions

Explore recent and relevant literature in Research Assistant →

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

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

limitedSLC9A9-related susceptibility to autismLOFAD

This gene — mechanism propensity

0.80top 10%

GOF

0.80top 10%

LOF

0.1993th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

146 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

Likely Pathogenic1

VUS93

Likely Benign21

Benign14

Conflicting1

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	0	0	0	1
Likely Pathogenic	1	0	0	0	1
VUS	5	85	2	1	93
Likely Benign	0	4	3	14	21
Benign	0	2	3	9	14
Conflicting	—				1
Total	7	91	8	24	131

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

21 pathogenic / likely-pathogenic (of 25) ClinVar copy-number / structural variants overlap SLC9A9 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →