DNAJC12

DnaJ heat shock protein family (Hsp40) member C12, the group of DNAJ (HSP40) heat shock proteins

Basic information

Region (hg38): 10:67796668-67838188

Links

ENSG00000108176 ∙ NCBI:56521 ∙ OMIM:606060 ∙ HGNC:28908 ∙ Uniprot:Q9UKB3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hyperphenylalaninemia due to DNAJC12 deficiency (Strong), mode of inheritance: AR
• hyperphenylalaninemia due to DNAJC12 deficiency (Supportive), mode of inheritance: AR
• hyperphenylalaninemia due to DNAJC12 deficiency (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hyperphenylalaninemia, mild, non-BH4-deficient	AR	Biochemical	The condition can involve variable neurocognitive dysfunction, and individuals have been reported as benefiting from neurotrnsmitter precursors, especially if initiated in infancy	Biochemical	28132689; 28794131; 29174366; 30139987

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DNAJC12 gene.

• not provided (86 variants)
• Inborn genetic diseases (11 variants)
• Hyperphenylalaninemia due to DNAJC12 deficiency (7 variants)
• DNAJC12-related condition (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DNAJC12 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				8	5	13
missense			33	3	2	38
nonsense	4					4
start loss		1				1
frameshift	1	2				3
inframe indel						0
splice donor/acceptor (+/-2bp)	2	1				3
splice region			2		1	3
non coding				12	12	24
Total	7	4	33	23	19

Highest pathogenic variant AF is 0.000223

Variants in DNAJC12

This is a list of pathogenic ClinVar variants found in the DNAJC12 region.

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

Position	Type	Phenotype	Significance	ClinVar
10-67796974-T-C			Benign (Jul 27, 2018)
10-67797044-A-G			Benign (Mar 29, 2019)
10-67797117-C-A		Hyperphenylalaninemia due to DNAJC12 deficiency	Pathogenic (Nov 01, 2019)
10-67797121-T-G			Uncertain significance (Jul 03, 2022)
10-67797124-C-T		Inborn genetic diseases	Uncertain significance (Nov 15, 2022)
10-67797134-G-A			Likely benign (Sep 03, 2018)
10-67797141-C-G		Inborn genetic diseases	Uncertain significance (Jan 31, 2023)
10-67797171-C-G		Inborn genetic diseases	Uncertain significance (Feb 26, 2024)
10-67797174-C-T		Inborn genetic diseases	Uncertain significance (Jun 05, 2023)
10-67797175-G-A			Uncertain significance (May 11, 2023)
10-67797189-C-T		Hyperphenylalaninemia due to DNAJC12 deficiency • Inborn genetic diseases • DNAJC12-related disorder	Pathogenic (Jan 02, 2024)
10-67797196-T-C		Inborn genetic diseases	Uncertain significance (Jan 18, 2024)
10-67797210-C-A			Uncertain significance (Apr 17, 2023)
10-67797218-GGAAA-G			Likely benign (Jun 17, 2021)
10-67797487-A-G			Benign (Jul 29, 2018)
10-67799811-AGGCGGAGGTTGCAGTGAGCCAGGATCACGCCACTGCACTCCAGCCTGGGCGACAGAGCGAGACTGTCAAAAAAAAAAAAATGTAGTTTCTAGTTAGGGTTCCCGTAGAAATAGACATGCAGACAAGAACTTGAAACAGGTTGGGCACAGTGGCCCACACCTATAATCCCAGCACTTTGGGAGGCTGAGGCCAATGGATCACTTGACCTCAGGAGTTTGAGACCAGCCTGGGCAACATGGCGAAACCCCATCTCTATAAAAAATTAGCCGGATGTGGTGGTGCACACCTGCAGTCCCAGCCATTTGGGGGCGGAGGTGGGAGGATCATCTGAGCCTAGGAGGTCGAGGCTGCAGTGAGTCGTGATCACACCACTGCACTCCAGCCTGGGTGACAGAGAGAGACTCTATCTCAAAAAAAAAAAAAAAAAAAAAAAAAATTGAAACAAAGTGGCTAATTTGGGAGGTAATCCCAGGTGGCACCTTAGCAGAATGAGAACCAAAGCTATAAAAGGTACATTATCAAACAAGTTACTGCCATGGGTAACTGCAAATGATCCCACTGGGGAACCCTGGGAGATAATATAAAACTTCTTAGAGTTATCTCACATGAGGGGTGAAGGACCTGGAGAATTTAGCTTCCCACTTCCACTCATTATTGTCATCCAAAGGGCATTTACTCCCTGACACTTACTGCCTGCTGATTTGCTGCCAAGTAGGCTCCATTGCCAGAGCAAGCCCTCTGGCAGAGTCACAATGTTTGTGGCTGGAGCCACAAGGTTGGCAATGCCTAGGAAGGTAGTGCCCAGGGACACGGCAGCACACCAAAATCATTGCGTACATTTAAATTTTTCTTGGTGGGACGCGGCGGCTCATGCCTGTAATCCCAGTGCTTTGGTGGGCCGAGGTGGGCAGATCACGAGGTCAGGAGTTCGAGACCAGCCTGGCCAACATGGTGAAACTCCGTCTCTACTAAAAACACAAAAAATTAGCCGGGCATGATGGCAGGTGCCGTAATCCCAGCTACTTGGCAGGCTGAGGCAGGAGAATAGCTTGACCCGGGAGGCAGAGGTTGCAGTGAGCCGAGGTGGTGCCACTGCACTCCAGCCTGGGCAACAAAGCAAGATTCTGTCTAAAAAAAAAAAAAATTTCTTTCTCTTTTTTACTCCAAGATGTTACACAAAACTATTTTATTTTAGAACTGTATTTATCAGAAGACATATTTATTGCATATTTAAGCAGAAAGAAAGTAAAAATGAGATTGTCTCGCACAGTGGTTTTCAGATGCAGTGCTCCATATTTTACTTTTTGCAATAAAGAATTAGAATGTGGTGGGGGCTATTTGGTGGCTGCTCATCACAGAAGAGACATCAAAAGGCAAATTCCAAAGTGAATATCTAGCACTGCTTGAGGAAATTAGCAAATATGCTGAAAAGTAATATATAAGAAGCCACTCAGGGCTTGGTAAAGTTGACAGGAATAATATTTCTTAAATGCTGACATTATAAAAATTTACGCTGCAGTAAAATGAAATCATAAATAATCATGCAACAGCACTTTGATATATCCAACTCCAGCTTTAAGGCACTAGTCAGAAAAGCCAATAATCTTTTAAACAGCATAAAGAAAATACTTGTAAATGCAACCTTTGGCAGAATTTCATAATTCTCCAACAACAGCTTTTTAGAACAATGATTCCCAGTTGGATGCAATGGCTCATGTCTGTAATCTTAGCACTTTGGGAGGCCAAAGTGGGCAGATCACCTGAGGTCAGGAGTTCTAAACCAGCCTGGGCAACATGGTGAAACCCCATCTCTACTAAAAATATGAAAATTAGCCAGGTGTGGTGGCGGGTGCCTGTAATCCCAGCTACTTGGGAGGCTGAGGCAGGAGAATCTCTTGAACCCAGGAGGTGGAGGTTGCAGTGAGCCGAGACAGTGCCACTGCACTCCAGCCTGGGCAACAAGAGCAAAACTCTGTTTCAAAAAAAAAAAAAAGAACAATGATTCCCATCCCCTCCACTTCATTCTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTGACACGGAGACACAGGGTCTTGCTCTATCACCCAGGCTGGAGTGCAGTGGCAGGATCATAGCTCACTGCAGCTTCAAACTCCCAGGCTCAAGTAATCCTTCTGCCTCAGCCTCCCAAGTAGCTGGAACTACAGGCGCACGCCAGCATACCTAGCTAATGGTTTTTTAATTTTGTGGAGACAGGGCTCTTGCTATGTTGCTCAAGCTGGTCTCGAACTCCTGGACTCAAGCGATCCTCCCATCTCAGCCTCCCAAAGTTCTAGGAGTACAGGCCCAAGCCACTGCAGCTGGCTCCACTTCATTCTTAAACAATAGCATACATATCACAATATGAAGACATCAAAACTGGCATCACAATTTGTTCTGAGTAAATTATATGTGAAAATTGATTATATGAATTGGCATTATCTGTTATTACCCAAGTAAATTAGAGCCGAGAACCAGGGAGAGGAAAAGAAAAGCACTCAGGACACAAATGCCTACCCAAGAATTCTATCACAAGCCAGCTGCCGAAATGACCTGCCTTGCCTCTAAGGCTAGTTTTACCTATTGCCATCACTCACCAATTACAGCTTGCTAGCTCCCAGAACTTTGCTAGTGCCAATGAGTTTTCTTTCATAACAATATGTAACATTTCTCTTTCTAATAAAACCCCCAACATTTTATTTGTTCTTCAGACACACCAAAGACCATCCCATCTGTGTGTATGCCTTGAATTGCAATGTAGTTTTTATATATTTTCCCAAGTAAAATGTTTTACATAGAGATTCGAATCTATATTTTTGTTTGACTTTGACATAACATATATCTACACTGTGGAATGTTATCAGCTGTTAAAAAGCAGGAATTCATTCTGAATGTAAGGATTTAAAGAGAAGTCTCTTAATAATAAAAGTTAACACTAAAAAAAGTGTTTACAATGTGCCTGGTATTGGTCTAAATATTTTACGTATATTAAGTTATTGTGCGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGACAGGATCTCATTCTGTCACCCAGGCTGGAGTACAGTGGTGCAATCGCAGCTCACTGCAGCCTCAACATCCCCCCCCACACACACACCCGGGCTCAAGTAACGGGATTACAGGCACGCACCACCACTCCTGGCTAATTTTCATATTTTTTTTTAGAGATGGTTTCACCATGTTGCCCAGGCTGGTCTCAAACTCCCGGCCTCAAGCAATCCGCCCACCTCACCCTCCCTAATTGCTAGGACTACAGGTGTGAGCCACTGCGCCTGGACAATTAAGTTATTTACTCCTCAAAAAAAAAAATTTTATGAGGTAGACACTAATATTTTGACCATTATATAACTAAGAAGACATAGATGCAGAGGGGTTAACTAGCTTGTCCAAGGTCATACAACTCATCAGTGAAAAGCTGAGCCCACATTCTTAACCACTGCGTAACACAGAGAAATGTGTACAGTATAACCCCATTCTTTACTTTTAAAGCTCTCATAAGTGCACATATACACACCTGTGTTAGCATAGAGAATAGTGGAAGGAAACACACCTGAGTGTCAGCCTTGGTTACTTCAAGAAACAGAAGCAGAGAAGGTTGGCAACCTGGCTATATATGATTCTTTGAATTTTTTAACAGCAAGTCTATACTACTTTTGTTTTTATTCAGTATCTAAATTACTATTTTTTTAAAAAGAAGGAAAATTTCGTAGAATCCTATGAGAGGGGCTCAAGAGGCCTCAGCATCATGCCTGAGTCTCTGAAGTGTCTCCCACCCACACTACACCTAATTTTGGTGTGCACAGACTTGGTCTGAATCTGACAGAAACAGAAAGACTTGGGGAACCCCCAGGGGTTCAAGAAACACAGAACTGAACATTCATCGTGTTTACATGTAGGGGAGTGATTGTACTCCTGTGTTTGCTTAAAACACTGTTTTTCTACACTTCAGGCTTCTCCTTTGATCAGTTTGTTAAATTATAACCATTTCCAGTTACTGGGTGATGCAATCAATGTGCAGACTCCACAGCCATCTCTTGGGTAACCAACAGAGACATCTGAATCAAACTCTATGGATCTTCATTCCCAGCAAGAAGAGAAGATGTAAAAGTTCTCCCCAAAGAGAGATTTGAAGTGACTATTTCTCAAAAGACTATAATCCACCACAAGCCATCTAACTATCTTCTTTTGAATACAAGTGTTCTAGGGTGTTCAGGAACGTTCTGCTTAAAGGCTAAATTCTAATAGGGTGCTACATCACAACCCTGAGAATCAACACATAATAATTTGAAGGACAGTTACAATGTGTGTATACAATGTGTGTATATACAACACATCCAAACTAGTTGGATGGCTAGATAGATAGCCAGCCAGATAGACAAATGATACAAACAGGTAACATTTACCTAGGGCTTCCTAGAGGTGAACCGCTGTGCTAAGCATTTTTTATGTATCTCCCCATTTAATCCTCATGGTAACCCTATAAGAAGGTACTATTTTTTATTTAAGAGATGGAGTCTCACTATGTCACCCAGGATGGAATGCAAGCACCTAATCACAGGAGTGATCATCACACACAGCAGCTTTGAACTCCTGGCCTCAAGCCAGCCTCCTGCCTCAGCCTCTTGAGTAGCTAGGACTACAGGTGCACAACAATGCACCTAGATGAGCAAGTACTATTATAATCCCTATTTTATAGATGCAGAAACTGAGGTCTAGAGAAGTTAAGTAACTTTGCCAAGTAATACAGATAATAAGTAGTAGAGCTAGGATGTGAACTCAGGTAGTGTAGCTTGGTAGCCAGGAGGTAAACTTCTATAATACTCTGCTTCAGTGGATTTATAAATGATTCAGAATGTCTACAGAGCTATTTACAGATAAGGCATTATTGGGCCGGGCATGGTGGCTTACACCTGTAATCCCAGCACTTTGGGAGGCCCAGGCAGGAGGATCACCTGAGGTCAGGAGTTTGAGACCAGCCTGGCCAACATGATGAAACCCCATCTCTACTAAAAATACAAAAATTAGCCAGGCATCATGGCAGGCGCCTGTAGTCCCAGCTACTGGGGAATCTGAGGCACAAGAATCACTTGAACCCAGGAGGCAGAGGTTGCAATGAGCTGAGATTATGCCACTGCACTCCAGCCTAGATGACAGAGTGAGACTCCATCTCAAAAAAGAAAAAAAATTAAATTCAATTCAATAAGGCATTATCATAGGATAGGGCAATGCCTTGGAACACTGACTGAAGTCAACCTGCCTTGGTTCAGACCCCTTTCCCTTCCCATACAAGCTGTATGGCTTTAAGCAAATTATTCAACCTCCTGGCCTTTGGTTTTCTCATCTATAAAATGAGAATAATATTGATATCAGCCTCACAAGCTTGTAGTGAGAATAAGTTAATATATATAAAATTAATATTAAATGAGATAATAAATGTAAACTAATATATGTAAAGAGTGTTCCTGCACATAGTAAACATTCAATCAATGTTAGCTAGCATTATGTCAGTAAAGCCAAAGACACTGAGAATTGTCTCAAGGTTTCCCTTCTGAGGAATACCTTCTAGTTTCGGTGTCAATGCTAAGTGTCTTTTAAGATGATAAACCAATCTTTAAACTTGGCACTGCTGTGCAGATTGAAAAAGTTAAGAATAAATGCAATATAAACAAAACTCTTTAATTTCAGACCTTCTCCATTCTGCAGTTATATAACGTGACTTACCTGAAGAATCTGAATTTTGCGGGGAGACTGACTTCTCTAGGGGCTTGGGTTCTTTCTGCTCCGTTTTCTCTGCGGTTGAAGCCAGCTCCTCTTTCTTTCTTTCTCTTTGCTCATTACATTCCTCATTTTCCATCTTGGTGGTATGAGTCTTGTCAGATTCTTCCAGCATCAGGTCTTTTTTACCTCTGACAACCCAGTGCATTGACTAAATTAATGTAAAGCAGAGATATAAAAATTAAATTGATATTATATGATTTTCTATATTTAAAGTTTGATATGTGGTAACACCTGACCTACTACTGTAGTGCTAATTAACAGCATGTTAGACTTGACTATTAACAAGATACTCATAAATTAATCCAGATATTAATTAATCCAACTATTAATAGTTACTTTTCACCATACACCCTTTTGTACCTTTTTCATTTTCTGTTCTGTATATGTATTTCCTATTAGATCTAAAAATTGGACAGATGGATGAATGAATGGAGGGATGGATGGATGAACTAACAAATGAATACAGTGAAAAAGAGCGCTTTTGAGTTTGCTGTATCAAGAATATTTCAAGTGGAATCATTAGCCCTACCATCAACCAAAATAATGCATAACTATTTCTTAAAACCTCATCGGGATATTGTGGGAAGCTATTCCTGAAGTACTAAGAAACAGTGACACACTACCTCTATTACCACAACTCAAGACTAGAAGGAAACATAGCCTTTAACACCCTAAAATTATAAATATTCTAGCTCTCTGCCCTAATCAAATCAAAGAAGTCATTTATTCCCACCTTCAACCTATCTCTTCCCAACTACAAAGAAGTGTCATCCTGAATCCTCTTCTCCAAATATAACCAGTCCAAAGGCTAATCAACCCCAAGATCCAAGAACCACCCCATAAAGCAGTCATTGCCACCAATAAATGTAACCAGCTCTCACCCTAACAAGAAAAAGAAAAGAGGCTGGGCACAGTGGCTCATGCTTGTAATCCCAGCACTTTGGGAAGCCAAGGTGGGTGGATCATTTGAGGCAAGGAGTTCGAGACCATCCTTGGCCAACAAGGTGAAACCACGTCTCTACTAAAAATACAAAAATTAGCTGGTCGTGGTGGTGCACACCTGTAATCCCAGCTACTCAGGAGGCTGAGGCGGGAGAATTGCTTGAACCCAGGAG-A		Hyperphenylalaninemia due to DNAJC12 deficiency	Pathogenic (Mar 07, 2017)
10-67805451-T-C			Benign (Apr 22, 2021)
10-67805469-A-G			Benign (Apr 22, 2021)
10-67805532-A-G			Benign (Apr 22, 2021)
10-67805564-G-A			Likely benign (Jan 07, 2024)
10-67805564-G-C			Likely benign (Jun 09, 2023)
10-67805574-G-A			Likely benign (Jan 23, 2024)
10-67805582-C-G		Hyperphenylalaninemia due to DNAJC12 deficiency	Pathogenic (Dec 02, 2022)
10-67805582-C-T			Pathogenic (May 27, 2022)
10-67805601-G-A			Pathogenic (Jul 21, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DNAJC12	protein_coding	protein_coding	ENST00000225171	5	41498

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000207	0.477	125681	0	65	125746	0.000258

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0635	104	106	0.983	0.00000560	1298
Missense in Polyphen		28	28.689	0.97597		385
Synonymous	0.0825	37	37.6	0.983	0.00000195	339
Loss of Function	0.686	10	12.6	0.792	6.85e-7	142

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00105	0.00105
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.000231	0.000231
European (Non-Finnish)	0.000176	0.000176
Middle Eastern	0.000109	0.000109
South Asian	0.0000982	0.0000980
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Disease: DISEASE: Hyperphenylalaninemia, mild, non-BH4-deficient (HPANBH4) [MIM:617384]: An autosomal recessive disorder characterized by increased serum phenylalanine, normal BH4 metabolism, and highly variable neurologic defects, including movement abnormalities and intellectual disability. {ECO:0000269|PubMed:28132689}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.0954

Intolerance Scores

• loftool: 0.898
• rvis_EVS: 0.31
• rvis_percentile_EVS: 72.23

Haploinsufficiency Scores

• pHI: 0.169
• hipred: N
• hipred_score: 0.216
• ghis: 0.470

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.270

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dnajc12

Gene ontology

• Cellular component: cytoplasm
• Molecular function: protein binding