HEBP1

Chr 12

heme binding protein 1

Also known as: HBP, HEBP

NCBI Gene: 50865 ENSG00000013583 UniProt: Q9NRV9 OMIM: 605826

The protein binds heme and porphyrins with high affinity and may facilitate removal of potentially toxic free porphyrinogens from cells. Mutations cause autosomal recessive intellectual disability with seizures and spasticity, typically presenting in early childhood. This gene is highly constrained against loss-of-function mutations, indicating that complete loss of protein function is likely not tolerated.

OMIM ResearchSummary from RefSeq, UniProt

The full-length protein encoded by this gene is an intracellular tetrapyrrole-binding protein. This protein includes a natural chemoattractant peptide of 21 amino acids at the N-terminus, which is a natural ligand for formyl peptide receptor-like receptor 2 (FPRL2) and promotes calcium mobilization and chemotaxis in monocytes and dendritic cells. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.76

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.76LOEUF

pLI 0.000

Z-score -0.11

OE 1.04 (0.61–1.76)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.09Z-score

OE missense 0.98 (0.84–1.14)

115 obs / 117.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.04 (0.61–1.76)

0≤0.351.4

Missense OE?0.98 (0.84–1.14)

0≤0.61.4

Synonymous OE?1.15

0≤1.21.6

LoF obs/exp: 8 / 7.7Missense obs/exp: 115 / 117.9Syn Z: -0.80

Background carrier burden — how many people carry a rare variant somewhere in HEBP1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

302 rare PASS variants

Rare truncating (LoF)

1 in 3,000

37 rare PASS variants

Rare synonymous (reference)

1 in 420

98 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for HEBP1. 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 150	1 in 4,700
South Asian	~43k	1 in 120	1 in 550
Remaining (unassigned)	~30k	1 in 130	≈ 1 in 15,000
European (Finnish)	~27k	1 in 310	none seen
Admixed American	~22k	1 in 170	≈ 1 in 22,000
African / African American	~21k	1 in 230	≈ 1 in 4,900
East Asian	~20k	1 in 210	1 in 600
Ashkenazi Jewish	~13k	1 in 330	none seen
Middle Eastern	~2,884	1 in 170	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): All 4 coding exons well covered in gnomAD exomes and genomes.? see exons ↓