GCHFR

Chr 15

GTP cyclohydrolase I feedback regulator

Also known as: GFRP, HsT16933, P35

NCBI Gene: 2644 ENSG00000137880 UniProt: P30047 OMIM: 602437

GTP cyclohydrolase I feedback regulatory protein binds to and mediates tetrahydrobiopterin inhibition of GTP cyclohydrolase I. The regulatory protein, GCHFR, consists of a homodimer. It is postulated that GCHFR may play a role in regulating phenylalanine metabolism in the liver and in the production of biogenic amine neurotransmitters and nitric oxide. [provided by RefSeq, Jul 2008]

OMIM Research

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.69

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.69LOEUF

pLI 0.048

Z-score 0.63

OE 0.62 (0.25–1.69)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.33Z-score

OE missense 0.87 (0.68–1.12)

42 obs / 48.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.62 (0.25–1.69)

0≤0.351.4

Missense OE?0.87 (0.68–1.12)

0≤0.61.4

Synonymous OE?1.23

0≤1.21.6

LoF obs/exp: 2 / 3.2Missense obs/exp: 42 / 48.5Syn Z: -0.81

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

gnomAD v4 · ~727k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 690

117 rare PASS variants

Rare truncating (LoF)

1 in 3,600

38 rare PASS variants

Rare synonymous (reference)

1 in 1,400

51 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GCHFR. 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)	~554k	1 in 600	1 in 3,700
South Asian	~42k	1 in 2,200	1 in 4,500
Remaining (unassigned)	~30k	1 in 1,600	1 in 790
European (Finnish)	~27k	1 in 1,900	≈ 1 in 26,000
Admixed American	~22k	1 in 1,600	≈ 1 in 21,000
African / African American	~21k	1 in 1,100	1 in 2,300
East Asian	~19k	1 in 1,300	≈ 1 in 4,700
Ashkenazi Jewish	~13k	≈ 1 in 4,200	≈ 1 in 12,000
Middle Eastern	~2,866	≈ 1 in 940	none seen

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): 2 of 3 coding exons well covered in gnomAD exomes; exon 2 marginal. Genomes: all 3.? see exons ↓