ANKK1

Chr 11

ankyrin repeat and kinase domain containing 1

Also known as: PKK2, sgK288

NCBI Gene: 255239 ENSG00000170209 UniProt: Q8NFD2

The protein encoded by this gene belongs to the Ser/Thr protein kinase family, and protein kinase superfamily involved in signal transduction pathways. This gene is closely linked to DRD2 gene (GeneID:1813) on chr 11, and a well studied restriction fragment length polymorphism (RFLP) designated TaqIA, was originally associated with the DRD2 gene, however, later was determined to be located in exon 8 of ANKK1 gene (PMIDs: 18621654, 15146457), where it causes a nonconservative amino acid substitution. It is not clear if this gene plays any role in neuropsychiatric disorders previously associated with Taq1A RFLP. [provided by RefSeq, Sep 2009]

Research

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.16

LOEUF

Multiple*

Mechanism· predicted

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?

1.16LOEUF

pLI 0.000

Z-score 0.93

OE 0.80 (0.56–1.16)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.01Z-score

OE missense 1.00 (0.92–1.08)

426 obs / 426.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.80 (0.56–1.16)

0≤0.351.4

Missense OE?1.00 (0.92–1.08)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 20 / 25.0Missense obs/exp: 426 / 426.7Syn Z: 0.25

Background carrier burden — how many people carry a rare variant somewhere in ANKK1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 35

1,092 rare PASS variants

Rare truncating (LoF)

1 in 150

136 rare PASS variants

Rare synonymous (reference)

1 in 83

435 rare PASS variants

Rare missense and truncating variants are carried at similar rates in ANKK1; this gene does not show strong loss-of-function constraint by this measure. 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 42	1 in 240
South Asian	~43k	1 in 34	1 in 390
Remaining (unassigned)	~30k	1 in 32	1 in 260
European (Finnish)	~27k	1 in 98	1 in 1,800
Admixed American	~22k	1 in 29	1 in 280
African / African American	~21k	1 in 36	1 in 560
East Asian	~20k	1 in 49	1 in 1,200
Ashkenazi Jewish	~13k	1 in 220	1 in 2,600
Middle Eastern	~2,884	1 in 27	1 in 210

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 8 coding exons well covered in gnomAD exomes and genomes.? see exons ↓