DNAJC21

DnaJ heat shock protein family (Hsp40) member C21, the group of DNAJ (HSP40) heat shock proteins

Basic information

Region (hg38): 5:34929558-34958964

Links

ENSG00000168724 ∙ NCBI:134218 ∙ OMIM:617048 ∙ HGNC:27030 ∙ Uniprot:Q5F1R6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Shwachman-Diamond syndrome (Supportive), mode of inheritance: AR
• bone marrow failure syndrome 3 (Moderate), mode of inheritance: AR
• bone marrow failure syndrome 3 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Bone marrow failure syndrome 3	AR	Hematologic; Oncologic	Individuals have been described with bone marrow failure, and awareness may allow prompt recognition and management related to hematologic (eg, anemia) and infectious sequelae; An individual has been described with AML, and awareness may allow prompt diagnosis and management; BMT has been described	Audiologic/Otolaryngologic; Craniofacial; Dental; Dermatologic; Hematologic; Musculoskeletal; Neurologic; Oncologic	27346687; 28062395; 29700810

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DNAJC21 gene.

• not provided (277 variants)
• not specified (26 variants)
• Inborn genetic diseases (25 variants)
• Bone marrow failure syndrome 3 (16 variants)
• DNAJC21-related condition (5 variants)
• Bone marrow failure syndrome 3;Shwachman-Diamond syndrome 1 (2 variants)
• Shwachman-Diamond syndrome 1;Bone marrow failure syndrome 3 (2 variants)
• 7 conditions (1 variants)
• Inherited bone marrow failure syndrome (1 variants)
• Shwachman-Diamond syndrome 1 (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DNAJC21 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			4	43	8	55
missense	1		125	4	3	133
nonsense	6	1				7
start loss						0
frameshift	11	1	3	1		16
inframe indel			3			3
splice donor/acceptor (+/-2bp)		5			1	6
splice region			6	11		17
non coding			9	39	3	51
Total	18	7	144	87	15

Highest pathogenic variant AF is 0.0000263

Variants in DNAJC21

This is a list of pathogenic ClinVar variants found in the DNAJC21 region.

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

Position	Type	Phenotype	Significance	ClinVar
5-34929647-AC-A			Uncertain significance (May 01, 2022)
5-34929813-T-G		DNAJC21-related disorder	Likely benign (Jun 13, 2023)
5-34929825-G-A			Likely benign (Sep 09, 2023)
5-34929831-C-T			Likely benign (Oct 04, 2023)
5-34929832-T-G			Uncertain significance (Dec 02, 2022)
5-34929834-T-G			Pathogenic (Dec 03, 2022)
5-34929840-G-T			Likely benign (Jan 03, 2024)
5-34929842-T-G			Uncertain significance (Dec 11, 2023)
5-34929844-G-A			Uncertain significance (Mar 13, 2022)
5-34929847-G-T			Uncertain significance (Aug 24, 2023)
5-34929851-G-C			Uncertain significance (Dec 27, 2021)
5-34929851-G-T		Inborn genetic diseases	Uncertain significance (Dec 26, 2023)
5-34929854-GC-AG			Uncertain significance (Aug 31, 2022)
5-34929862-A-C			Uncertain significance (Oct 19, 2020)
5-34929869-A-G		not specified	Likely benign (Jan 12, 2024)
5-34929869-A-T		DNAJC21-related disorder	Uncertain significance (Jan 12, 2024)
5-34929870-G-A			Likely benign (Dec 09, 2023)
5-34929876-C-T			Likely benign (Feb 22, 2023)
5-34929913-C-G		Bone marrow failure syndrome 3 • Inherited bone marrow failure syndrome	Pathogenic (Jul 28, 2016)
5-34929915-G-T			Uncertain significance (Mar 18, 2022)
5-34929917-G-C			Likely pathogenic (Aug 09, 2022)
5-34929917-G-T			Likely pathogenic (Mar 24, 2023)
5-34929920-A-G			Uncertain significance (Jul 14, 2022)
5-34929921-G-A			Benign/Likely benign (Jan 06, 2024)
5-34929928-T-A			Likely benign (Aug 23, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DNAJC21	protein_coding	protein_coding	ENST00000382021	13	29372

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.10e-7	0.999	125593	0	155	125748	0.000616

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.255	303	316	0.960	0.0000168	3859
Missense in Polyphen		59	72.003	0.81941		918
Synonymous	-0.0619	111	110	1.01	0.00000622	944
Loss of Function	2.87	17	35.4	0.480	0.00000186	435

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00113	0.00113
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000492	0.000489
Finnish	0.000277	0.000277
European (Non-Finnish)	0.000842	0.000835
Middle Eastern	0.000492	0.000489
South Asian	0.000229	0.000229
Other	0.00131	0.00114

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May act as a co-chaperone for HSP70. May play a role in ribosomal RNA (rRNA) biogenesis, possibly in the maturation of the 60S subunit. Binds the precursor 45S rRNA. {ECO:0000269|PubMed:27346687}.

Recessive Scores

• pRec: 0.104

Intolerance Scores

• loftool: 0.958
• rvis_EVS: -0.15
• rvis_percentile_EVS: 42.23

Haploinsufficiency Scores

• pHI: 0.137
• hipred: N
• hipred_score: 0.379
• ghis: 0.562

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.358

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dnajc21
• 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)

Gene ontology

• Biological process: protein folding
• Cellular component: nucleolus;ribosome
• Molecular function: RNA binding;protein binding;zinc ion binding