CYB5D2

protein-coding

cytochrome b5 domain containing 2, the group of Membrane associated progesterone receptor family

Gene summary

Predicted to enable heme binding activity and steroid binding activity. Predicted to be involved in nervous system development. Predicted to act upstream of or within positive regulation of neuron differentiation. Predicted to be located in extracellular region. Predicted to be active in endomembrane system and membrane. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_144611.4

Inheritance

—

ClinVar variants

U:56B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.84

Max pathogenic AF

—

Genomic locus

chr17:4,143,168-4,187,310

External References & Databases

Ensembl (ENSG00000167740)

Transcript & Mutation Effects

hg38 • Region Span ~44.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CYB5D2 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 58

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_144611.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous						0
missense			55 clinvar	4 clinvar		59
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	56	4	0	60

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 15 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_144611.4	RefSeq	NP_653212.1	4	MANE Select
ENST00000301391.8	Ensembl	ENSP00000301391.4	4	MANE Select
NM_001254755.2	RefSeq	NP_001241684.1	3	Standard
NM_001254756.1	RefSeq	NP_001241685.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

positive regulation of neuron differentiation

Molecular Function

heme binding

Cellular Component

extracellular region

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000301391
Coding exons: 4
Length: 44144
Individuals with no LoFs: 125642
Homozygous LoFs: 1
Heterozygous LoFs: 105
Defined: 125748
p: 0.000422

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.606	193	171	1.13	0.00000969	1679
Missense (PolyPhen)		48	45.801	1.048		453
Synonymous	-0.955	88	77.3	1.14	0.00000503	568
Loss of Function	0.475	9	10.7	0.843	5.41e-7	114

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00071	0.00071	rare
Finnish	0.0015	0.0015	notable
European (Non-Finnish)	0.00026	0.00025	rare
South Asian	0.00069	0.00069	rare
Other	0.00099	0.00081	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Heme-binding protein which promotes neuronal but not astrocyte differentiation. {ECO:0000250}.;

Recessive Scores

pRec: 0.215

Intolerance Scores

LoFtool: 0.508
RVIS EVS: -0.6
RVIS percentile EVS: 17.91

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.278

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium