AHSP

protein-coding

alpha hemoglobin stabilizing protein

Gene summary

This gene encodes a molecular chaperone which binds specifically to free alpha-globin and is involved in hemoglobin assembly. The encoded protein binds to monomeric alpha-globin until it has been transferred to beta-globin to form a heterodimer, which in turn binds to another heterodimer to form the stable tetrameric hemoglobin. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

Previous symbols:

ERAF

MANE transcript

NM_016633.4

Inheritance

—

ClinVar variants

U:16B:3

Top phenotype

AHSP-related disorder

gnomAD constraint

pLI —, LoF o/e 2.2

Max pathogenic AF

—

Genomic locus

chr16:31,527,900-31,528,803

External References & Databases

Ensembl (ENSG00000169877)

Transcript & Mutation Effects

hg38 • Region Span ~0.9 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 AHSP variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 14

not providedTotal: 5

AHSP-related disorderTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_016633.4. 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				2 clinvar		2
missense			16 clinvar	1 clinvar		17
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	16	3	0	19

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_016633.4	RefSeq	NP_057717.1	2	MANE Select
ENST00000302312.9	Ensembl	ENSP00000307199.4	2	MANE Select
NM_001318221.2	RefSeq	NP_001305150.1	2	Standard
NM_001318222.2	RefSeq	NP_001305151.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

hemoglobins chaperone

Biological Process

protein folding
hemoglobin metabolic process
hemopoiesis
erythrocyte differentiation
protein stabilization

Molecular Function

protein binding
hemoglobin binding
unfolded protein binding

Cellular Component

cytoplasm
hemoglobin complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000302312
Coding exons: 2
Length: 940
Individuals with no LoFs: 125736
Homozygous LoFs: 0
Heterozygous LoFs: 12
Defined: 125748
p: 0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.248	59	53.9	1.10	0.00000290	668
Missense (PolyPhen)		14	12.991	1.0777		188
Synonymous	-0.131	24	23.2	1.03	0.00000128	197
Loss of Function	-1.50	4	1.82	2.20	7.71e-8	23

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000070	0.000070	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Acts as a chaperone to prevent the harmful aggregation of alpha-hemoglobin during normal erythroid cell development. Specifically protects free alpha-hemoglobin from precipitation. It is predicted to modulate pathological states of alpha-hemoglobin excess such as beta-thalassemia. {ECO:0000269|PubMed:12066189}.;

Recessive Scores

pRec: 0.119

Intolerance Scores

LoFtool: 0.700
RVIS EVS: 0.41
RVIS percentile EVS: 76.67

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.731

Gene Damage Prediction

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