DHTKD1

Protein identityUniProt · HPA

UniProt accession

Q96HY7

Gene

DHTKD1

Ensembl

ENSG00000181192

Chromosome

10

Canonical length

919 aa

Protein class

Disease related genes, Human disease related genes, Metabolic proteins, Plasma proteins, Predicted intracellular proteins

Subcellular location

Mitochondria

OverviewNCBI Gene

This gene encodes a component of a mitochondrial 2-oxoglutarate-dehydrogenase-complex-like protein involved in the degradation pathways of several amino acids, including lysine. Mutations in this gene are associated with 2-aminoadipic 2-oxoadipic aciduria and Charcot-Marie-Tooth Disease Type 2Q. [provided by RefSeq, May 2013]

Canonical amino-acid sequenceUniProt

919 residues, UniProt reviewed canonical sequence.

>Q96HY7|DHTKD1
     1  MASATAAAAR RGLGRALPLF WRGYQTERGV YGYRPRKPES REPQGALERP PVDHGLARLV
    61  TVYCEHGHKA AKINPLFTGQ ALLENVPEIQ ALVQTLQGPF HTAGLLNMGK EEASLEEVLV
   121  YLNQIYCGQI SIETSQLQSQ DEKDWFAKRF EELQKETFTT EERKHLSKLM LESQEFDHFL
   181  ATKFSTVKRY GGEGAESMMG FFHELLKMSA YSGITDVIIG MPHRGRLNLL TGLLQFPPEL
   241  MFRKMRGLSE FPENFSATGD VLSHLTSSVD LYFGAHHPLH VTMLPNPSHL EAVNPVAVGK
   301  TRGRQQSRQD GDYSPDNSAQ PGDRVICLQV HGDASFCGQG IVPETFTLSN LPHFRIGGSV
   361  HLIVNNQLGY TTPAERGRSS LYCSDIGKLV GCAIIHVNGD SPEEVVRATR LAFEYQRQFR
   421  KDVIIDLLCY RQWGHNELDE PFYTNPIMYK IIRARKSIPD TYAEHLIAGG LMTQEEVSEI
   481  KSSYYAKLND HLNNMAHYRP PALNLQAHWQ GLAQPEAQIT TWSTGVPLDL LRFVGMKSVE
   541  VPRELQMHSH LLKTHVQSRM EKMMDGIKLD WATAEALALG SLLAQGFNVR LSGQDVGRGT
   601  FSQRHAIVVC QETDDTYIPL NHMDPNQKGF LEVSNSPLSE EAVLGFEYGM SIESPKLLPL
   661  WEAQFGDFFN GAQIIFDTFI SGGEAKWLLQ SGIVILLPHG YDGAGPDHSS CRIERFLQMC
   721  DSAEEGVDGD TVNMFVVHPT TPAQYFHLLR RQMVRNFRKP LIVASPKMLL RLPAAVSTLQ
   781  EMAPGTTFNP VIGDSSVDPK KVKTLVFCSG KHFYSLVKQR ESLGAKKHDF AIIRVEELCP
   841  FPLDSLQQEM SKYKHVKDHI WSQEEPQNMG PWSFVSPRFE KQLACKLRLV GRPPLPVPAV
   901  GIGTVHLHQH EDILAKTFA

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against DHTKD1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.22

Highest tissue expression

121 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about DHTKD1.

Disease | AllUniProt

Conditions DHTKD1 is implicated in, by any mechanism.

• Charcot-Marie-Tooth disease, axonal, type 2Q (CMT2Q) MIM:615025
• Alpha-aminoadipic and alpha-ketoadipic aciduria (AAKAD) MIM:204750

Disease | GeneticClinVar

61 pathogenic / likely-pathogenic of 1,057 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• 2-aminoadipic 2-oxoadipic aciduria
• Charcot-Marie-Tooth disease axonal type 2Q
• DHTKD1-related disorder
• Charcot-Marie-Tooth disease type 2A2
• Inborn genetic diseases

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.25

gnomAD pLI

0

gnomAD missense Z

-0.12

DepMap mean gene effect

0

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 7% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• generation of precursor metabolites and energy
• glycolytic process
• hematopoietic progenitor cell differentiation

Molecular functions

• thiamine pyrophosphate binding
• 2-oxoadipate dehydrogenase activity

Cellular components

• mitochondrial matrix
• mitochondrion
• oxoadipate dehydrogenase complex

Protein domainsUniProt · Pfam · InterPro

• Dehydrogenase, E1 component
• Transketolase-like, pyrimidine-binding domain
• 2-oxoglutarate dehydrogenase E1 component
• Thiamin diphosphate-binding fold
• 2-oxoglutarate dehydrogenase E1 component/KDG, C-terminal
• Multifunctional 2-oxoglutarate metabolism enzyme, C-terminal domain superfamily
• Dehydrogenase E1 component
• Transketolase, pyrimidine binding domain
• 2-oxoglutarate dehydrogenase C-terminal

KeywordsUniProt

• Charcot-Marie-Tooth disease
• Glycolysis
• Mitochondrion
• Neurodegeneration
• Neuropathy
• Oxidoreductase
• Thiamine pyrophosphate
• Transit peptide

InteractionsUniProt · HPA

Protein binding partners of DHTKD1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• DLST