HSPA9

heat shock protein family A (Hsp70) member 9, the group of Heat shock 70kDa proteins|Small nucleolar RNA protein coding host genes

Basic information

Region (hg38): 5:138553756-138575675

Previous symbols: [ "HSPA9B" ]

Links

ENSG00000113013 ∙ NCBI:3313 ∙ OMIM:600548 ∙ HGNC:5244 ∙ Uniprot:P38646 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal dominant sideroblastic anemia (Strong), mode of inheritance: AD
• autosomal dominant sideroblastic anemia (Moderate), mode of inheritance: AR
• even-plus syndrome (Limited), mode of inheritance: AR
• autosomal recessive sideroblastic anemia (Supportive), mode of inheritance: AR
• even-plus syndrome (Supportive), mode of inheritance: AR
• even-plus syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Anemia, sideroblastic 4; Even-Plus syndrome	AD	Cardiovascular; Hematologic; Renal	Individuals with anemia have been described with anemia requiring RBC transfusions in some individuals, and awareness may allow for surveillance and prompt management; EVEN-plus syndrome may involve congenital anomalies (eg, cardiac anomalies) that require early identification and interventions for management	Cardiovascular; Craniofacial; Dermatologic; Gastrointestinal; Hematologic; Musculoskeletal	3653362; 26491070; 26598328

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HSPA9 gene.

• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HSPA9 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				14	2	16
missense		1	22	1	1	25
nonsense	1					1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)		1				1
splice region				3	1	4
non coding				1	2	3
Total	1	2	22	16	5

Variants in HSPA9

This is a list of pathogenic ClinVar variants found in the HSPA9 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
5-138556060-C-G		Inborn genetic diseases	Uncertain significance (Aug 08, 2022)
5-138556101-C-T		Inborn genetic diseases	Uncertain significance (Apr 07, 2022)
5-138556104-T-C		Inborn genetic diseases	Uncertain significance (Jan 29, 2024)
5-138556470-G-A			Likely benign (Oct 01, 2022)
5-138556481-G-A		Even-plus syndrome	Conflicting classifications of pathogenicity (Aug 25, 2023)
5-138556500-G-A		HSPA9-related disorder	Likely benign (Mar 12, 2019)
5-138556533-G-A			Benign (Dec 31, 2019)
5-138556549-A-G		Inborn genetic diseases	Uncertain significance (Feb 28, 2023)
5-138556782-C-A		Inborn genetic diseases	Uncertain significance (Oct 29, 2021)
5-138557400-A-C			Likely pathogenic (Oct 09, 2020)
5-138557409-C-T		Inborn genetic diseases	Uncertain significance (Apr 25, 2022)
5-138557411-C-G			Likely benign (Feb 08, 2018)
5-138557993-T-G		HSPA9-related disorder	Likely benign (May 24, 2019)
5-138557995-A-C			Likely benign (Dec 31, 2019)
5-138558545-TA-T		HSPA9-related disorder	Benign (Dec 31, 2019)
5-138558559-A-G		HSPA9-related disorder	Likely benign (Apr 25, 2018)
5-138558563-T-C		Inborn genetic diseases	Uncertain significance (May 20, 2024)
5-138558642-C-T		HSPA9-related disorder	Uncertain significance (May 01, 2023)
5-138559873-C-T			Likely benign (Nov 15, 2018)
5-138559895-CTATTAA-C		Autosomal dominant sideroblastic anemia	Uncertain significance (Jul 01, 2024)
5-138559927-A-G			Likely benign (Nov 01, 2023)
5-138559944-A-T		Inborn genetic diseases	Uncertain significance (Oct 04, 2022)
5-138560024-A-G		Inborn genetic diseases	Uncertain significance (May 05, 2023)
5-138561584-G-C		Inborn genetic diseases	Uncertain significance (Feb 28, 2023)
5-138561607-A-G			Likely benign (Aug 01, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HSPA9	protein_coding	protein_coding	ENST00000297185	17	20563

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.969	0.0315	125702	0	46	125748	0.000183

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.04	312	368	0.848	0.0000200	4447
Missense in Polyphen		87	148.71	0.58503		2008
Synonymous	-0.267	133	129	1.03	0.00000677	1346
Loss of Function	4.74	6	37.2	0.161	0.00000225	420

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000213	0.000213
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.000185	0.000185
European (Non-Finnish)	0.000282	0.000281
Middle Eastern	0.000109	0.000109
South Asian	0.0000980	0.0000980
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Chaperone protein which plays an important role in mitochondrial iron-sulfur cluster (ISC) biogenesis. Interacts with and stabilizes ISC cluster assembly proteins FXN, NFU1, NFS1 and ISCU (PubMed:26702583). Regulates erythropoiesis via stabilization of ISC assembly (PubMed:21123823, PubMed:26702583). May play a role in the control of cell proliferation and cellular aging (By similarity). {ECO:0000250|UniProtKB:P38647, ECO:0000269|PubMed:21123823, ECO:0000269|PubMed:26702583}.
• Disease: DISEASE: Anemia, sideroblastic, 4 (SIDBA4) [MIM:182170]: A form of sideroblastic anemia, a bone marrow disorder defined by the presence of pathologic iron deposits in erythroblast mitochondria. Sideroblastic anemia is characterized by anemia of varying severity, hypochromic peripheral erythrocytes, systemic iron overload secondary to chronic ineffective erythropoiesis, and the presence of bone marrow ringed sideroblasts. Sideroblasts are characterized by iron-loaded mitochondria clustered around the nucleus. SIDBA4 has been reported to be inherited as an autosomal recessive disease, with a pseudodominant pattern of inheritance in some families. {ECO:0000269|PubMed:26491070}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Even-plus syndrome (EVPLS) [MIM:616854]: An autosomal recessive syndrome characterized by epiphyseal and vertebral dysplasia, prenatal-onset short stature, a distinct craniofacial phenotype with microtia, a flat facial profile with flat nose and triangular nares, cardiac malformations, and additional findings such as anal atresia, hypodontia, aplasia cutis, and others. {ECO:0000269|PubMed:26598328}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: RNA degradation - Homo sapiens (human);Tuberculosis - Homo sapiens (human);Parkin-Ubiquitin Proteasomal System pathway;Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation;Regulation of HSF1-mediated heat shock response;Cellular responses to stress;Metabolism of proteins;Cellular responses to external stimuli;Cellular response to heat stress;Mitochondrial protein import (Consensus)

Recessive Scores

• pRec: 0.734

Intolerance Scores

• loftool: 0.423
• rvis_EVS: -0.85
• rvis_percentile_EVS: 11.06

Haploinsufficiency Scores

• pHI: 0.624
• hipred: Y
• hipred_score: 0.800
• ghis: 0.639

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.835

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hspa9
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; immune system phenotype

Zebrafish Information Network

• Gene name: hspa9
• Affected structure: blood cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: response to unfolded protein;iron-sulfur cluster assembly;erythrocyte differentiation;cellular response to heat;cellular response to unfolded protein;interleukin-12-mediated signaling pathway;protein refolding;negative regulation of apoptotic process;regulation of erythrocyte differentiation;negative regulation of erythrocyte differentiation;chaperone cofactor-dependent protein refolding
• Cellular component: nucleolus;cytoplasm;mitochondrion;mitochondrial matrix;focal adhesion;mitochondrial nucleoid;extracellular exosome
• Molecular function: RNA binding;protein binding;ATP binding;ATPase activity;heat shock protein binding;ubiquitin protein ligase binding;ATPase activity, coupled;protein folding chaperone;unfolded protein binding;misfolded protein binding