ANKRD42

Chr 11

ankyrin repeat domain 42

Also known as: PPP1R79, SARP

NCBI Gene: 338699 ENSG00000137494 UniProt: Q8N9B4 OMIM: 619778

The protein is predicted to bind NF-kappaB and inhibit cyclin-dependent protein kinases, acting to positively regulate NF-kappaB transcription and inflammatory cytokine production in the nucleus. This gene is extremely intolerant to loss-of-function variation (pLI near 1.0), indicating mutations likely cause severe developmental disorders, though specific associated phenotypes have not yet been established in clinical databases. The high constraint suggests mutations would be expected to cause early-onset neurodevelopmental abnormalities.

OMIM ResearchSummary from RefSeq

Predicted to enable NF-kappaB binding activity and cyclin-dependent protein serine/threonine kinase inhibitor activity. Predicted to act upstream of or within obsolete positive regulation of NF-kappaB transcription factor activity and positive regulation of cytokine production involved in inflammatory response. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.23

LOEUF

GOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.23LOEUF

pLI 0.000

Z-score 0.76

OE 0.82 (0.56–1.23)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.13Z-score

OE missense 0.97 (0.87–1.09)

205 obs / 210.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.82 (0.56–1.23)

0≤0.351.4

Missense OE?0.97 (0.87–1.09)

0≤0.61.4

Synonymous OE?0.88

0≤1.21.6

LoF obs/exp: 17 / 20.7Missense obs/exp: 205 / 210.5Syn Z: 0.78

Background carrier burden — how many people carry a rare variant somewhere in ANKRD42?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 68

756 rare PASS variants

Rare truncating (LoF)

1 in 370

144 rare PASS variants

Rare synonymous (reference)

1 in 300

229 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ANKRD42. 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 81	1 in 880
South Asian	~43k	1 in 81	1 in 360
Remaining (unassigned)	~30k	1 in 88	1 in 220
European (Finnish)	~27k	1 in 190	1 in 2,300
Admixed American	~22k	1 in 81	1 in 240
African / African American	~21k	1 in 67	1 in 400
East Asian	~20k	1 in 59	1 in 280
Ashkenazi Jewish	~13k	1 in 320	1 in 2,100
Middle Eastern	~2,884	1 in 62	1 in 260

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 11 coding exons well covered in gnomAD exomes and genomes.? see exons ↓