HBD

protein-coding

hemoglobin subunit delta, the group of Hemoglobin subunits

Gene summary

The delta (HBD) and beta (HBB) genes are normally expressed in the adult: two alpha chains plus two beta chains constitute HbA, which in normal adult life comprises about 97% of the total hemoglobin. Two alpha chains plus two delta chains constitute HbA-2, which with HbF comprises the remaining 3% of adult hemoglobin. Five beta-like globin genes are found within a 45 kb cluster on chromosome 11 in the following order: 5'-epsilon--Ggamma--Agamma--delta--beta-3'. Mutations in the delta-globin gene are associated with beta-thalassemia. [provided by RefSeq, Jul 2008]

MANE transcript

NM_000519.4

Inheritance

ClinVar variants

P:10U:53B:2

Top phenotype

delta-beta-thalassemia

gnomAD constraint

pLI —, LoF o/e 1.53

Max pathogenic AF

—

Genomic locus

chr11:5,232,678-5,243,657

External References & Databases

Ensembl (ENSG00000223609)

Transcript & Mutation Effects

hg38 • Region Span ~11.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

delta-beta-thalassemiaSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0016489

Submitter: Orphanet

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to HBD variants in ClinVar

51 Conditions Cataloged

not specifiedTotal: 14

not providedTotal: 9

Fetal hemoglobin quantitative trait locus 1Total: 7

delta ThalassemiaTotal: 5

ThalassemiaTotal: 4

Hemoglobin Lepore traitTotal: 3

HBD-related disorderTotal: 3

Delta-0-thalassemiaTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000519.4. 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			4 clinvar	1 clinvar	1 clinvar	6
missense	4 clinvar		48 clinvar			52
nonsense	1 clinvar					1
start loss						0
frameshift	1 clinvar					1
splice donor/acceptor (+/-2bp)	4 clinvar		1 clinvar			5
Total	10	0	53	1	1	65

Highest pathogenic variant AF is 0.0018738242

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 9 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000519.4	RefSeq	NP_000510.1	3	MANE Select
ENST00000650601.1	Ensembl	ENSP00000497529.1	3	MANE Select
ENST00000292901.7	Ensembl	ENSP00000292901.3	3	Standard
ENST00000292901.8	Ensembl	ENSP00000292901.3	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

blood coagulation
oxygen transport
hydrogen peroxide catabolic process
protein heterooligomerization
cellular oxidant detoxification

Molecular Function

peroxidase activity
oxygen carrier activity
protein binding
oxygen binding
heme binding

Cellular Component

cytosol
hemoglobin complex
haptoglobin-hemoglobin complex
blood microparticle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000380299
Coding exons: 3
Length: 2693
Individuals with no LoFs: 125716
Homozygous LoFs: 0
Heterozygous LoFs: 21
Defined: 125737
p: 0.0000835

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.01	99	74.4	1.33	0.00000365	956
Missense (PolyPhen)		30	21.824	1.3746		336
Synonymous	-0.884	36	29.9	1.21	0.00000142	299
Loss of Function	-0.966	6	3.93	1.53	1.69e-7	49

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00011	0.00011	rare
South Asian	0.00016	0.00016	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in oxygen transport from the lung to the various peripheral tissues.;

Intolerance Scores

LoFtool: 0.138
RVIS EVS: 0.48
RVIS percentile EVS: 79.04

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.334

Gene Damage Prediction

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