HYKK

Chr 15

hydroxylysine kinase

Also known as: AGPHD1

NCBI Gene: 123688 ENSG00000188266 UniProt: A2RU49 OMIM: 614681

Enables hydroxylysine kinase activity. Predicted to be involved in obsolete lysine catabolic process. Predicted to be located in mitochondrial matrix. Implicated in chronic obstructive pulmonary disease. [provided by Alliance of Genome Resources, Jun 2026]

OMIM Research

OMIM ResearchGenerating clinical summary…

Clinical highlights

Gene–disease validity (ClinGen)

Refuted · inborn disorder of lysine and hydroxylysine metabolism · UD · ClinGen 2023

evidence has disproved this relationship

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.15

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.15LOEUF

pLI 0.000

Z-score 1.16

OE 0.68 (0.41–1.15)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.67Z-score

OE missense 0.87 (0.76–0.98)

171 obs / 197.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.68 (0.41–1.15)

0≤0.351.4

Missense OE?0.87 (0.76–0.98)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 10 / 14.8Missense obs/exp: 171 / 197.6Syn Z: -0.06

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

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 140

436 rare PASS variants

Rare truncating (LoF)

1 in 590

69 rare PASS variants

Rare synonymous (reference)

1 in 230

159 rare PASS variants

Rare missense and truncating variants are carried at similar rates in HYKK; 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 170	1 in 690
South Asian	~43k	1 in 130	1 in 500
Remaining (unassigned)	~30k	1 in 110	1 in 840
European (Finnish)	~27k	1 in 480	1 in 1,600
Admixed American	~22k	1 in 120	1 in 2,800
African / African American	~21k	1 in 150	1 in 970
East Asian	~20k	1 in 130	1 in 1,500
Ashkenazi Jewish	~13k	1 in 470	none seen
Middle Eastern	~2,884	1 in 110	≈ 1 in 2,900

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): 3 of 4 coding exons well covered in gnomAD exomes; exon 3 marginal. Genomes: all 4.? see exons ↓