HSPA4L

protein-coding

heat shock protein family A (Hsp70) member 4 like, the group of Heat shock 70kDa proteins

Gene summary

The protein encoded by this gene is heat shock inducible and may act as a chaperone. The encoded protein can protect the heat-shocked cell against the harmful effects of aggregated proteins. This gene is highly expressed in leukemia cells and may be a good target for therapeutic intervention. Several transcripts encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2015]

MANE transcript

NM_014278.4

Inheritance

—

ClinVar variants

U:104B:10

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.42

Max pathogenic AF

—

Genomic locus

chr4:127,781,821-127,840,733

External References & Databases

Ensembl (ENSG00000164070)

Transcript & Mutation Effects

hg38 • Region Span ~58.9 kb

Loading mutation effect viewer...

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 HSPA4L variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 99

not providedTotal: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014278.4. 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	3 clinvar	2 clinvar	7
missense			98 clinvar	5 clinvar		103
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	104	8	2	114

Loading ClinVar variants...

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_014278.4	RefSeq	NP_055093.2	19	MANE Select
ENST00000296464.9	Ensembl	ENSP00000296464.3	19	MANE Select
NM_001317381.2	RefSeq	NP_001304310.1	20	Standard
NM_001317382.2	RefSeq	NP_001304311.1	19	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Protein processing in endoplasmic reticulum - Homo sapiens (human)
Regulation of HSF1-mediated heat shock response
Cellular responses to stress
Cellular responses to external stimuli
Cellular response to heat stress

Biological Process

protein folding
response to unfolded protein

Molecular Function

ATP binding

Cellular Component

nucleus
cytoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000296464
Coding exons: 19
Length: 58913
Individuals with no LoFs: 125705
Homozygous LoFs: 0
Heterozygous LoFs: 41
Defined: 125746
p: 0.000163

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.00	372	431	0.864	0.0000208	5576
Missense (PolyPhen)		109	140.2	0.77747		1731
Synonymous	1.27	128	148	0.868	0.00000738	1479
Loss of Function	3.53	18	43.0	0.419	0.00000215	580

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.00013	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00017	0.00017	rare
South Asian	0.00040	0.00039	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Possesses chaperone activity in vitro where it inhibits aggregation of citrate synthase. {ECO:0000250}.;

Recessive Scores

pRec: 0.162

Intolerance Scores

LoFtool: 0.842
RVIS EVS: 0.24
RVIS percentile EVS: 69.51

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.351

Gene Damage Prediction

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