DNAJC19

Summary

DNAJC19 (DnaJ heat shock protein family (Hsp40) member C19, HGNC:30528) is a protein-coding gene on chromosome 3q26.33, encoding Mitochondrial import inner membrane translocase subunit TIM14 (Q96DA6). Mitochondrial co-chaperone which forms a complex with prohibitins to regulate cardiolipin remodeling. It is a selective cancer dependency (DepMap: 26.9% of cell lines).

The protein encoded by this gene is thought to be part of a complex involved in the ATP-dependent transport of transit peptide-containing proteins from the inner cell membrane to the mitochondrial matrix. Defects in this gene are a cause of 3-methylglutaconic aciduria type 5 (MGA5), also known as dilated cardiomyopathy with ataxia (DCMA). Alternative splicing of this gene results in multiple transcript variants. Related pseudogenes have been identified on chromosomes 1, 2, 6, 10, 14 and 19.

Source: NCBI Gene 131118 — RefSeq curated summary.

At a glance

• Gene–disease (curated): 3-methylglutaconic aciduria type 5 (Definitive, ClinGen)
• GWAS associations: 5
• Clinical variants (ClinVar): 176 total — 13 pathogenic, 8 likely-pathogenic
• Phenotypes (HPO): 52
• Cancer dependency (DepMap): dependent in 26.9% of screened cell lines
• MANE Select transcript: NM_145261

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30528
Approved symbol	DNAJC19
Name	DnaJ heat shock protein family (Hsp40) member C19
Location	3q26.33
Locus type	gene with protein product
Status	Approved
Aliases	TIMM14, Tim14, Pam18
Ensembl gene	ENSG00000205981
Ensembl biotype	protein_coding
OMIM	608977
Entrez	131118

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 7 protein_coding, 3 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000382564, ENST00000469657, ENST00000472504, ENST00000478723, ENST00000479269, ENST00000482363, ENST00000485675, ENST00000486355, ENST00000491873, ENST00000643241, ENST00000646965, ENST00000688055, ENST00000928270

RefSeq mRNA: 2 — MANE Select: NM_145261 NM_001190233, NM_145261

CCDS: CCDS33895, CCDS54684

Canonical transcript exons

ENST00000382564 — 6 exons

Exon	Start	End
ENSE00001492636	180983709	180984710
ENSE00001856072	180989600	180989736
ENSE00003488653	180985926	180985996
ENSE00003599055	180986943	180987022
ENSE00003627139	180988023	180988096
ENSE00003654383	180988178	180988229

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 98.21.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 74.1842 / max 1139.9815, expressed in 1826 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
45747	73.0875	1826
45746	0.9017	446
45748	0.1949	56

Top tissues by expression

256 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	98.21	gold quality
tendon	UBERON:0000043	97.88	gold quality
calcaneal tendon	UBERON:0003701	97.71	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.44	gold quality
left ventricle myocardium	UBERON:0006566	96.87	gold quality
tibialis anterior	UBERON:0001385	96.41	gold quality
muscle of leg	UBERON:0001383	96.32	gold quality
heart left ventricle	UBERON:0002084	96.16	gold quality
gastrocnemius	UBERON:0001388	96.07	gold quality
cardiac ventricle	UBERON:0002082	96.06	gold quality
deltoid	UBERON:0001476	95.90	gold quality
apex of heart	UBERON:0002098	95.75	gold quality
quadriceps femoris	UBERON:0001377	95.65	gold quality
left adrenal gland	UBERON:0001234	95.63	gold quality
left adrenal gland cortex	UBERON:0035825	95.63	gold quality
kidney epithelium	UBERON:0004819	95.59	gold quality
vastus lateralis	UBERON:0001379	95.47	gold quality
right adrenal gland	UBERON:0001233	95.46	gold quality
heart	UBERON:0000948	95.38	gold quality
skeletal muscle tissue	UBERON:0001134	95.37	gold quality
heart right ventricle	UBERON:0002080	95.26	gold quality
right adrenal gland cortex	UBERON:0035827	95.26	gold quality
right atrium auricular region	UBERON:0006631	95.21	gold quality
myocardium	UBERON:0002349	95.19	gold quality
biceps brachii	UBERON:0001507	95.15	gold quality
prefrontal cortex	UBERON:0000451	95.07	gold quality
cardiac atrium	UBERON:0002081	95.05	gold quality
muscle tissue	UBERON:0002385	94.91	gold quality
adrenal tissue	UBERON:0018303	94.85	gold quality
adrenal cortex	UBERON:0001235	94.83	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-6108	no	306.19
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

36 targeting DNAJC19, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-2116-3P	99.74	64.32	889
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-298	99.63	67.56	1916
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-1252-3P	99.55	67.71	2862
HSA-MIR-154-3P	99.50	70.05	831
HSA-MIR-487A-3P	99.50	69.95	840
HSA-MIR-122B-5P	99.46	70.81	1457
HSA-MIR-4312	99.34	67.30	511
HSA-MIR-892C-5P	99.16	70.56	2116
HSA-MIR-485-5P	99.10	64.78	1889
HSA-MIR-6884-5P	99.10	64.50	1987
HSA-MIR-29A-5P	99.08	68.59	1813
HSA-MIR-522-3P	98.91	68.56	1817

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 26.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 6)

• The association of dilated cardiomyopathy with ataxia (DCMA) syndrome with a segment of 3q26.33 and the identification of a splice mutation in a novel gene DNAJC19 in DCMA patients. (PMID:16055927)
• Dilated cardiomyopathy caused by homozygous mutations in a novel gene, DNAJC19, presumed to play a role in importation of mitochondrial proteins. (PMID:17244376)
• A report of a new mutation in the human DNAJC19 gene that causes early onset dilated cardiomyopathy syndrome in two brothers of Finnish origin. (PMID:22797137)
• The loss of DNAJC19/PHB complexes affects cardiolipin acylation and leads to the accumulation of cardiolipin species with altered acyl chains. (PMID:24856930)
• Both DnaJC15 and DnaJC19 formed two distinct subcomplexes with Magmas at the import channel. (PMID:27330077)
• Mutations in DNAJC19 cause altered mitochondrial structure and increased mitochondrial respiration in human iPSC-derived cardiomyocytes. (PMID:38142971)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	dnajc19	ENSDARG00000044420
mus_musculus	Dnajc19	ENSMUSG00000027679
rattus_norvegicus	Dnajc19	ENSRNOG00000049819
drosophila_melanogaster	CG7394	FBGN0036173
caenorhabditis_elegans	dnj-21	WBGENE00001039

Paralogs (1): DNAJC15 (ENSG00000120675)

Protein

Protein identifiers

Mitochondrial import inner membrane translocase subunit TIM14 — Q96DA6 (reviewed: Q96DA6)

Alternative names: DnaJ homolog subfamily C member 19

All UniProt accessions (7): A0A0S2Z5X1, A0A2R8Y817, A0A2R8Y839, A0A8I5KQT8, Q96DA6, F2Z3A7, G5E9V2

UniProt curated annotations — full annotation on UniProt →

Function. Mitochondrial co-chaperone which forms a complex with prohibitins to regulate cardiolipin remodeling. May be a component of the PAM complex, a complex required for the translocation of transit peptide-containing proteins from the inner membrane into the mitochondrial matrix in an ATP-dependent manner. May act as a co-chaperone that stimulate the ATP-dependent activity.

Subunit / interactions. Interacts with PHB2; the interaction associates DNAJC19 with the prohibitin complex. Interacts with TIMM16/PAM16. May be a component of the PAM complex at least composed of a mitochondrial HSP70 protein, GRPEL1 or GRPEL2, TIMM44, TIMM16/PAM16 and TIMM14/DNAJC19.

Subcellular location. Mitochondrion inner membrane.

Tissue specificity. Ubiquitously expressed.

Disease relevance. 3-methylglutaconic aciduria 5 (MGCA5) [MIM:610198] An autosomal recessive disorder characterized by early-onset dilated cardiomyopathy, growth failure, cerebellar ataxia causing significant motor delays, testicular dysgenesis, growth failure and significant increases in urine organic acids, particularly 3-methylglutaconic acid and 3-methylglutaric acid. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the TIM14 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96DA6-1	1	yes
Q96DA6-2	2

RefSeq proteins (2): NP_001177162, NP_660304* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001623	DnaJ_domain	Domain
IPR036869	J_dom_sf	Homologous_superfamily

Pfam: PF00226

UniProt features (10 total): modified residue 3, topological domain 2, initiator methionine 1, chain 1, transmembrane region 1, domain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96DA6-F1	87.50	0.56

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (3): 2, 39, 70

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-1268020	Mitochondrial protein import

MSigDB gene sets: 245 (showing top): GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_PROTEIN_TARGETING, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_PHOSPHATIDYLGLYCEROL_METABOLIC_PROCESS, chr3q26, GOBP_REGULATION_OF_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, GOBP_REGULATION_OF_LIPID_METABOLIC_PROCESS, GOBP_PROTEIN_MATURATION, GOBP_REPRODUCTIVE_SYSTEM_DEVELOPMENT, GOBP_SENSORY_PERCEPTION_OF_LIGHT_STIMULUS, GOCC_MITOCHONDRIAL_ENVELOPE, GOBP_PROTEIN_FOLDING

GO Biological Process (8): protein folding (GO:0006457), obsolete protein targeting to mitochondrion (GO:0006626), intracellular protein transport (GO:0006886), visual perception (GO:0007601), protein import into mitochondrial matrix (GO:0030150), genitalia development (GO:0048806), regulation of cardiolipin metabolic process (GO:1900208), protein transport (GO:0015031)

GO Molecular Function (2): ATPase activator activity (GO:0001671), protein binding (GO:0005515)

GO Cellular Component (8): PAM complex, Tim23 associated import motor (GO:0001405), mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), TIM23 mitochondrial import inner membrane translocase complex (GO:0005744), membrane (GO:0016020), protein-containing complex (GO:0032991), inner mitochondrial membrane protein complex (GO:0098800), matrix side of mitochondrial inner membrane (GO:0099617)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Protein localization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular protein localization	2
inner mitochondrial membrane protein complex	2
mitochondrial inner membrane	2
cellular process	1
protein maturation	1
protein transport	1
intracellular transport	1
sensory perception of light stimulus	1
protein transmembrane import into intracellular organelle	1
protein localization to mitochondrion	1
import into the mitochondrion	1
mitochondrial protein import pathway	1
sex differentiation	1
animal organ development	1
reproductive structure development	1
cardiolipin metabolic process	1
regulation of phospholipid metabolic process	1
transport	1
establishment of protein localization	1
ATP-dependent activity	1
molecular function activator activity	1
binding	1
TIM23 mitochondrial import inner membrane translocase complex	1
mitochondrial matrix	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
cellular anatomical structure	1
cellular_component	1
membrane protein complex	1
mitochondrial protein-containing complex	1
lumenal side of membrane	1

Protein interactions and networks

STRING

1852 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DNAJC19	TIMM44	O43615	996
DNAJC19	PAM16	Q9Y3D7	995
DNAJC19	HSPA9	P30036	972
DNAJC19	TIMM17A	Q99595	954
DNAJC19	TIMM50	Q3ZCQ8	934
DNAJC19	AUH	Q13825	908
DNAJC19	TAFAZZIN	Q16635	893
DNAJC19	TIMM21	Q9BVV7	890
DNAJC19	HSPA4	P34932	887
DNAJC19	PHB2	Q99623	830
DNAJC19	DNAJB4	Q9UDY4	821
DNAJC19	PHB1	P35232	762
DNAJC19	TIMM17B	O60830	760
DNAJC19	GRPEL1	Q9HAV7	712
DNAJC19	TIMM9	Q9Y5J7	689

IntAct

77 interactions, top by confidence:

A	B	Type	Score
RANBP6	SLC27A2	psi-mi:“MI:0914”(association)	0.640
P2RX4	FAM20B	psi-mi:“MI:0914”(association)	0.640
SLC1A1	AGPAT2	psi-mi:“MI:0914”(association)	0.640
LPAR4	POTEF	psi-mi:“MI:0914”(association)	0.530
SLC15A1	METTL15	psi-mi:“MI:0914”(association)	0.530
SLC2A12	METTL15	psi-mi:“MI:0914”(association)	0.530
SPACA1	GOLIM4	psi-mi:“MI:0914”(association)	0.530
rep	AGPS	psi-mi:“MI:0914”(association)	0.530
TSPAN5	SC5D	psi-mi:“MI:0914”(association)	0.530
ERBB2	HAX1	psi-mi:“MI:0914”(association)	0.530
	HSPA9	psi-mi:“MI:0882”(atpase reaction)	0.440
TFAP2A	DNAJC19	psi-mi:“MI:0915”(physical association)	0.370
Cct2	OSBPL9	psi-mi:“MI:0914”(association)	0.350
FBXO31	CCNQ	psi-mi:“MI:0914”(association)	0.350
MAD2L2		psi-mi:“MI:0914”(association)	0.350
SLC39A12	POM121C	psi-mi:“MI:0914”(association)	0.350
PCDHGB1	FAM171A2	psi-mi:“MI:0914”(association)	0.350
TSPAN5	KLHL2	psi-mi:“MI:0914”(association)	0.350
SLC1A1	TNFRSF10B	psi-mi:“MI:0914”(association)	0.350
VNN2	ATP2A1	psi-mi:“MI:0914”(association)	0.350
P2RX4	ORC4	psi-mi:“MI:0914”(association)	0.350
SLC37A3	CYB5R3	psi-mi:“MI:0914”(association)	0.350
MFSD8	EBP	psi-mi:“MI:0914”(association)	0.350
MIX23	TAMM41	psi-mi:“MI:0914”(association)	0.350
COQ9	NDUFS8	psi-mi:“MI:0914”(association)	0.350
MAIP1	TIMM44	psi-mi:“MI:0914”(association)	0.350

BioGRID (238): DNAJC19 (Affinity Capture-MS), DNAJC19 (Affinity Capture-MS), DNAJC19 (Affinity Capture-MS), DNAJC19 (Affinity Capture-MS), DNAJC19 (Affinity Capture-MS), DNAJC19 (Affinity Capture-MS), DNAJC19 (Affinity Capture-MS), DNAJC19 (Affinity Capture-MS), DNAJC19 (Affinity Capture-MS), DNAJC19 (Affinity Capture-MS), DNAJC19 (Affinity Capture-MS), DNAJC19 (Affinity Capture-MS), DNAJC19 (Affinity Capture-MS), DNAJC19 (Affinity Capture-MS), DNAJC19 (Affinity Capture-MS)

ESM2 similar proteins: A5DGN9, A5DXK7, A8KB87, A8WM57, B4M693, C7ZKY9, O02161, O14225, O60084, O62250, P34339, P35180, P35848, P42949, P91454, Q01852, Q3ZBN8, Q4I375, Q4WI88, Q54QN1, Q54SV6, Q59W44, Q59ZW9, Q5ANP2, Q5B187, Q5B4H1, Q5RF34, Q60RS2, Q617M0, Q6BIY6, Q6BSN9, Q6BVY9, Q6BXP3, Q6C161, Q6C331, Q6CDV7, Q6CK35, Q6FT88, Q6PBT7, Q754J4

Diamond homologs: P42834, P91454, Q07914, Q3ZBN8, Q4I7T5, Q4WI88, Q54QN1, Q59SI2, Q5B4H1, Q5RCP4, Q5RF34, Q617M0, Q6BH37, Q6CEU0, Q6CNW2, Q6DDA1, Q6FPU1, Q6PBT7, Q759D2, Q78YY6, Q7RX75, Q8RV04, Q96DA6, Q9CQV7, Q9LYY2, Q9SF33, Q9UT37, Q9VTJ8, Q9Y5T4, A0A0D1E2P6, P42824, P42825, P43644, Q0JB88, Q94AW8, A4IR30, A9MXI3, B4T6D7, B4TIB5, B4TVZ6

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
DNAJC19	“form complex”	“TIM23 complex”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

176 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	13
Likely pathogenic	8
Uncertain significance	55
Likely benign	73
Benign	10

Top pathogenic / likely-pathogenic (21)

Variant ID	HGVS	Classification
120181	NM_145261.4(DNAJC19):c.300del (p.Ala101fs)	Pathogenic
1299515	NM_145261.4(DNAJC19):c.62dup (p.Tyr21Ter)	Pathogenic
1460139	NC_000003.11:g.(?180707368)(180707390_?)del	Pathogenic
1951	NM_145261.4(DNAJC19):c.130-1G>C	Pathogenic
2157602	NM_145261.4(DNAJC19):c.250C>T (p.Arg84Ter)	Pathogenic
2427336	NC_000003.11:g.(?180332709)(180707390_?)del	Pathogenic
3069178	NM_145261.4(DNAJC19):c.102del (p.Lys34fs)	Pathogenic
3646339	NM_145261.4(DNAJC19):c.122del (p.Pro41fs)	Pathogenic
3676557	NM_145261.4(DNAJC19):c.168dup (p.Lys57fs)	Pathogenic
3688402	NM_145261.4(DNAJC19):c.263del (p.Leu87_Leu88insTer)	Pathogenic
4760020	NM_145261.4(DNAJC19):c.29_32del (p.Leu10fs)	Pathogenic
937620	NM_145261.4(DNAJC19):c.63C>G (p.Tyr21Ter)	Pathogenic
958162	NM_145261.4(DNAJC19):c.51del (p.Phe17fs)	Pathogenic
1691439	NM_145261.4(DNAJC19):c.129+1G>A	Likely pathogenic
235279	NM_145261.4(DNAJC19):c.4-1G>A	Likely pathogenic
2717499	NM_145261.4(DNAJC19):c.280+1_280+5del	Likely pathogenic
2841822	NM_145261.4(DNAJC19):c.210-2A>G	Likely pathogenic
2990462	NM_145261.4(DNAJC19):c.4-24_15del	Likely pathogenic
3064132	NM_145261.4(DNAJC19):c.281-2A>C	Likely pathogenic
872142	NM_145261.4(DNAJC19):c.292dup (p.Tyr98fs)	Likely pathogenic
993012	NM_145261.4(DNAJC19):c.158G>A (p.Gly53Glu)	Likely pathogenic

SpliceAI

1032 predictions. Top by Δscore:

Variant	Effect	Δscore
3:180984711:C:CC	acceptor_gain	1.0000
3:180985529:T:A	donor_gain	1.0000
3:180985921:CTTA:C	donor_loss	1.0000
3:180985922:TTA:T	donor_loss	1.0000
3:180985923:TA:T	donor_loss	1.0000
3:180985924:A:AC	donor_gain	1.0000
3:180985924:AC:A	donor_gain	1.0000
3:180985924:ACCT:A	donor_loss	1.0000
3:180985925:C:CC	donor_gain	1.0000
3:180985925:CC:C	donor_gain	1.0000
3:180985925:CCT:C	donor_gain	1.0000
3:180985925:CCTT:C	donor_gain	1.0000
3:180985925:CCTTT:C	donor_gain	1.0000
3:180985992:TAGGG:T	acceptor_gain	1.0000
3:180985993:AGGG:A	acceptor_gain	1.0000
3:180985994:GGG:G	acceptor_gain	1.0000
3:180985995:GG:G	acceptor_gain	1.0000
3:180985995:GGCTA:G	acceptor_loss	1.0000
3:180985997:C:CA	acceptor_loss	1.0000
3:180985997:C:CC	acceptor_gain	1.0000
3:180985998:T:C	acceptor_loss	1.0000
3:180986001:T:TC	acceptor_gain	1.0000
3:180988021:A:AC	donor_gain	1.0000
3:180988022:C:CT	donor_gain	1.0000
3:180988022:CA:C	donor_gain	1.0000
3:180988022:CAG:C	donor_gain	1.0000
3:180988022:CAGA:C	donor_gain	1.0000
3:180988022:CAGAT:C	donor_gain	1.0000
3:180988054:A:AC	donor_gain	1.0000
3:180988055:C:CC	donor_gain	1.0000

AlphaMissense

748 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:180984675:C:G	A106P	1.000
3:180984707:C:T	G95E	1.000
3:180985936:A:C	H90Q	1.000
3:180985936:A:T	H90Q	1.000
3:180985937:T:C	H90R	1.000
3:180985938:G:C	H90D	1.000
3:180986955:A:T	I66K	1.000
3:180988195:G:T	A13D	1.000
3:180984670:T:A	K107N	0.999
3:180984670:T:G	K107N	0.999
3:180984671:T:A	K107I	0.999
3:180984674:G:T	A106D	0.999
3:180984679:A:C	N104K	0.999
3:180984679:A:T	N104K	0.999
3:180984683:A:T	I103N	0.999
3:180984685:T:A	K102N	0.999
3:180984685:T:G	K102N	0.999
3:180984690:C:G	A101P	0.999
3:180984707:C:A	G95V	0.999
3:180984708:C:G	G95R	0.999
3:180984708:C:T	G95R	0.999
3:180985931:T:A	D92V	0.999
3:180985932:C:G	D92H	0.999
3:180985934:G:T	P91H	0.999
3:180985938:G:T	H90N	0.999
3:180985939:A:C	N89K	0.999
3:180985939:A:T	N89K	0.999
3:180985958:C:G	R83P	0.999
3:180985962:G:C	H82D	0.999
3:180985965:C:G	A81P	0.999

dbSNP variants (sampled 300 via entrez): RS1000296018 (3:180985321 C>T), RS1000447572 (3:180984971 T>C), RS1000735624 (3:180986112 TG>T), RS1001857510 (3:180986571 C>A,T), RS1002848406 (3:180989749 C>A), RS1003806186 (3:180987675 C>T), RS1003850979 (3:180989532 C>G,T), RS1003922271 (3:180988022 C>T), RS1004814753 (3:180989061 G>A), RS1004860630 (3:180986835 CA>C,CAA), RS1005286480 (3:180988591 GAA>G), RS1005818168 (3:180990760 T>C), RS1007144893 (3:180986200 T>C), RS1007740943 (3:180989178 A>G), RS1008250368 (3:180988902 T>C)

Disease associations

OMIM: gene MIM:608977 | disease phenotypes: MIM:610198, MIM:250950, MIM:258501

GenCC curated gene-disease

Disease	Classification	Inheritance
3-methylglutaconic aciduria type 5	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
3-methylglutaconic aciduria type 5	Definitive	AR

Mondo (3): 3-methylglutaconic aciduria type 5 (MONDO:0012435), 3-methylglutaconic aciduria (MONDO:0017359), 3-methylglutaconic aciduria type 3 (MONDO:0009787)

Orphanet (3): Dilated cardiomyopathy with ataxia (Orphanet:66634), 3-methylglutaconic aciduria (Orphanet:289902), 3-methylglutaconic aciduria type 3 (Orphanet:67047)

HPO phenotypes

52 total (30 of 52 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000051	Perineal hypospadias
HP:0000648	Optic atrophy
HP:0000821	Hypothyroidism
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001256	Mild intellectual disability
HP:0001319	Neonatal hypotonia
HP:0001324	Muscle weakness
HP:0001332	Dystonia
HP:0001414	Microvesicular hepatic steatosis
HP:0001508	Failure to thrive
HP:0001510	Growth delay
HP:0001511	Intrauterine growth retardation
HP:0001631	Atrial septal defect
HP:0001635	Congestive heart failure
HP:0001644	Dilated cardiomyopathy
HP:0001645	Sudden cardiac death
HP:0001657	Prolonged QT interval
HP:0001998	Neonatal hypoglycemia
HP:0001999	Abnormal facial shape
HP:0002061	Lower limb spasticity
HP:0002151	Increased circulating lactate concentration
HP:0002194	Delayed gross motor development
HP:0002345	Action tremor
HP:0002376	Developmental regression
HP:0002470	Nonprogressive cerebellar ataxia
HP:0002910	Elevated circulating hepatic transaminase concentration

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST002539_51	Schizophrenia	2.000000e-08
GCST004946_22	Schizophrenia	6.000000e-14
GCST006803_33	Schizophrenia	3.000000e-12
GCST007201_230	Schizophrenia	9.000000e-09
GCST007201_232	Schizophrenia	2.000000e-11

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
C579867	3-Methylglutaconic Aciduria (supp.)
C565706	3-Methylglutaconic Aciduria, Type V (supp.)
C535311	Costeff optic atrophy syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

45 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
Arsenic	decreases expression, increases abundance, affects cotreatment, increases expression	3
Leflunomide	decreases expression	2
Acetaminophen	decreases expression, increases expression	2
Valproic Acid	affects expression, increases expression	2
Cyclosporine	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
bisphenol A	affects cotreatment, increases expression	1
sodium arsenate	decreases expression, increases abundance	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	decreases expression, affects cotreatment	1
nefazodone	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
corosolic acid	decreases expression	1
abrine	decreases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases reaction, increases expression	1
bisphenol S	affects methylation	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Atrazine	decreases expression	1
Vehicle Emissions	decreases reaction, increases expression	1
Chenodeoxycholic Acid	affects cotreatment, decreases expression	1
Deoxycholic Acid	affects cotreatment, decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Folic Acid	increases expression	1

Cellosaurus cell lines

4 cell lines: 3 induced pluripotent stem cell, 1 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D0PI	WAe007-A-3	Embryonic stem cell	Female
CVCL_ZL56	LIBUCi001-A	Induced pluripotent stem cell	Male
CVCL_ZL57	LIBUCi002-A	Induced pluripotent stem cell	Female
CVCL_ZL59	JMUi001-A-1	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

1 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford