NME3

Summary

NME3 (NME/NM23 nucleoside diphosphate kinase 3, HGNC:7851) is a protein-coding gene on chromosome 16p13.3, encoding Nucleoside diphosphate kinase C (Q13232). Catalyzes the transfer of a gamma-phosphoryl group from a nucleoside triphosphate, mainly ATP, to a nucleoside diphosphate via a ping-pong mechanism involving a phosphohistidine intermediate, therefore contributing to the nucleoside triphosphate homeostasis.

Enables nucleoside diphosphate kinase activity. Involved in DNA repair; mitochondrial fusion; and nucleoside triphosphate biosynthetic process. Located in mitochondrial outer membrane.

Source: NCBI Gene 4832 — RefSeq curated summary.

At a glance

• Gene–disease (curated): inherited neurodegenerative disorder (Limited, GenCC)
• Clinical variants (ClinVar): 22 total
• MANE Select transcript: NM_002513

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7851
Approved symbol	NME3
Name	NME/NM23 nucleoside diphosphate kinase 3
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Aliases	DR-nm23, NM23-H3, NDPKC
Ensembl gene	ENSG00000103024
Ensembl biotype	protein_coding
OMIM	601817
Entrez	4832

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 7 protein_coding, 6 retained_intron, 2 nonsense_mediated_decay

ENST00000219302, ENST00000561637, ENST00000563367, ENST00000563498, ENST00000563854, ENST00000564252, ENST00000564628, ENST00000565379, ENST00000566600, ENST00000567271, ENST00000568561, ENST00000904960, ENST00000904961, ENST00000904962, ENST00000933403

RefSeq mRNA: 1 — MANE Select: NM_002513 NM_002513

CCDS: CCDS10443

Canonical transcript exons

ENST00000219302 — 5 exons

Exon	Start	End
ENSE00000683466	1771280	1771410
ENSE00001273366	1771489	1771543
ENSE00002607212	1770320	1770766
ENSE00003510157	1771070	1771171
ENSE00003602518	1770881	1770993

Expression profiles

Bgee: expression breadth ubiquitous, 265 present calls, max score 98.31.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.3705 / max 106.4473, expressed in 1791 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
155859	20.5293	1788
155861	2.0380	814
155860	0.8031	555

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adenohypophysis	UBERON:0002196	98.31	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.81	gold quality
right adrenal gland	UBERON:0001233	97.62	gold quality
left adrenal gland cortex	UBERON:0035825	97.62	gold quality
pituitary gland	UBERON:0000007	97.56	gold quality
cerebellar hemisphere	UBERON:0002245	97.54	gold quality
right adrenal gland cortex	UBERON:0035827	97.54	gold quality
right uterine tube	UBERON:0001302	97.49	gold quality
cerebellar cortex	UBERON:0002129	97.45	gold quality
left adrenal gland	UBERON:0001234	97.44	gold quality
adrenal cortex	UBERON:0001235	96.93	gold quality
endocervix	UBERON:0000458	96.86	gold quality
mucosa of stomach	UBERON:0001199	96.68	gold quality
left uterine tube	UBERON:0001303	96.61	gold quality
mucosa of transverse colon	UBERON:0004991	96.60	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.60	gold quality
descending thoracic aorta	UBERON:0002345	96.53	gold quality
ascending aorta	UBERON:0001496	96.47	gold quality
thoracic aorta	UBERON:0001515	96.46	gold quality
left ovary	UBERON:0002119	96.42	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.41	gold quality
right ovary	UBERON:0002118	96.35	gold quality
right coronary artery	UBERON:0001625	96.33	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.32	gold quality
left coronary artery	UBERON:0001626	96.22	gold quality
cerebellum	UBERON:0002037	96.17	gold quality
right lobe of thyroid gland	UBERON:0001119	96.14	gold quality
aorta	UBERON:0000947	95.98	gold quality
left lobe of thyroid gland	UBERON:0001120	95.91	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.82	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.58
E-HCAD-13	yes	11.40

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TFAP2A

miRNA regulators (miRDB)

14 targeting NME3, 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-4795-3P	100.00	74.62	4024
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-3136-3P	99.57	66.59	781
HSA-MIR-7155-3P	99.57	66.48	794
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-6773-5P	97.04	64.30	595
HSA-MIR-6762-5P	96.55	64.62	972
HSA-MIR-6845-5P	96.55	64.65	969
HSA-MIR-6724-5P	96.41	63.11	507
HSA-MIR-3131	95.33	65.74	102
HSA-MIR-611	93.79	64.24	81
HSA-MIR-1247-5P	85.92	61.07	65

Literature-anchored findings (GeneRIF, showing 10)

• Among genes correlated to nodal metastatic progression, we verified in vitro that NM23-H3 reduced cell motility. (PMID:17900511)
• Down-regulated DR-nm23 expression is associated with invasion and metastasis in colorectal cancer. (PMID:23765094)
• Thus Tip60 interacts with RNR and NME3 to provide site-specific synthesis of dNTP for facilitating DNA repair in serum-deprived cells which contain low levels of dNTPs. (PMID:26945015)
• Proinflammatory signaling mediated by innate immunity engagement of flagellin-activated TLR5 in tumor cells results in antitumor effects through NME3 kinase, a positive downstream regulator of flagellin-mediated NFkappaB signaling, enhancing survival for several human cancers. (PMID:29523766)
• The ciliopathy-typical manifestations of NME3 depletion in two vertebrate in vivo models, the biochemical association of NME3 with validated NPHPs, and its localization to the basal body reveal a role for NME3 in ciliary function. We conclude that mutations in the NME3 gene may aggravate the ciliopathy phenotypes observed in humans. (PMID:30111592)
• Given the critical role of mitochondrial dynamics and energy requirements in neuronal development, the homozygous mutation in NME3 is linked to a fatal mitochondrial neurodegenerative disorder. (PMID:30587587)
• NME3 Regulates Mitochondria to Reduce ROS-Mediated Genome Instability. (PMID:32708927)
• Genetic defects in peroxisome morphogenesis (Pex11beta, dynamin-like protein 1, and nucleoside diphosphate kinase 3) affect docosahexaenoic acid-phospholipid metabolism. (PMID:36522796)
• NME3 binds to phosphatidic acid and mediates PLD6-induced mitochondrial tethering. (PMID:37584589)
• Mechanistic Insights into Substrate Recognition of Human Nucleoside Diphosphate Kinase C Based on Nucleotide-Induced Structural Changes. (PMID:39337255)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	nme3	ENSDARG00000100990
mus_musculus	Nme3	ENSMUSG00000073435
rattus_norvegicus	Nme3	ENSRNOG00000015749

Paralogs (8): NME8 (ENSG00000086288), NME4 (ENSG00000103202), NME5 (ENSG00000112981), NME7 (ENSG00000143156), NME6 (ENSG00000172113), NME9 (ENSG00000181322), NME1 (ENSG00000239672), NME2 (ENSG00000243678)

Protein

Protein identifiers

Nucleoside diphosphate kinase C — Q13232 (reviewed: Q13232)

Alternative names: DR-nm23, Nucleoside diphosphate kinase 3, nm23-H3

All UniProt accessions (5): Q13232, H3BMQ7, H3BPD9, H3BPR2, H3BRA8

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the transfer of a gamma-phosphoryl group from a nucleoside triphosphate, mainly ATP, to a nucleoside diphosphate via a ping-pong mechanism involving a phosphohistidine intermediate, therefore contributing to the nucleoside triphosphate homeostasis. In vitro, can also use other phosphate donors such as UTP and GTP. Independently of its nucleoside diphosphate kinase activity, involved in mitochondrial membrane tethering, a prerequisite for fusion through direct membrane-binding and hexamerization. Involved in DNA repair of both single- and double-stranded breaks by associating with the ribonucleotide reductase (RNR) complex via interaction with the histone acetyltransferase KAT5, facilitating recruitment to DNA damage sites independently of its kinase activity. Inhibits granulocyte differentiation. May be required for ciliary function during renal development.

Subunit / interactions. Homohexamer (PubMed:11277919, PubMed:30587587, PubMed:37584589, Ref.10). Heterohexamer with NME1. Interacts (via its N-terminal region) with KAT5; this interaction enables recruitment of NME3 at DNA damage sites where it plays a role in the repair of DNA. Found in association with several ciliary nephronophthisis proteins, including NEK8, CEP164, ANKS6.

Subcellular location. Mitochondrion outer membrane. Cytoplasm. Cytoskeleton. Cilium basal body.

Post-translational modifications. Autophosphorylation is Mg(2+)-dependent.

Disease relevance. A substitution in the initiation codon of the NME3 gene substitution (p.Met1Val), resulting in lack of full protein expression has been found in a female infant with an early-onset fatal neurodegenerative disorder.

Domain organisation. The N-terminal hydrophobic region (1-17) is critical for mitochondrial outer membrane targeting and phosphatidic acid binding.

Similarity. Belongs to the NDK family.

RefSeq proteins (1): NP_002504* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001564	Nucleoside_diP_kinase	Family
IPR023005	Nucleoside_diP_kinase_AS	Active_site
IPR034907	NDK-like_dom	Domain
IPR036850	NDK-like_dom_sf	Homologous_superfamily

Pfam: PF00334

Enzyme classification (BRENDA):

• EC 2.7.4.6 — nucleoside-diphosphate kinase (BRENDA: 102 organisms, 269 substrates, 41 inhibitors, 131 Km, 29 kcat entries)

Substrate kinetics (BRENDA)

20 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
GTP	0.07–5.5	22
ADP	0.024–1.26	17
ATP	0.005–4.6	14
DTDP	0.001–1.1	11
CTP	0.04–12	8
UTP	0.11–27	8
DCDP	0.01–0.56	6
GDP	0.02–0.049	5
UDP	0.1–0.28	5
TTP	0.89–5.28	4
8-BROMO-IDP	0.033–0.06	2
CDP	0.05–0.69	2
DGDP	0.14–0.25	2
DCTP	0.02	1
DGTP	0.041	1

Catalyzed reactions (Rhea), 5 shown:

• a ribonucleoside 5’-diphosphate + ATP = a ribonucleoside 5’-triphosphate + ADP (RHEA:18113)
• UDP + ATP = UTP + ADP (RHEA:25098)
• dTDP + ATP = dTTP + ADP (RHEA:27682)
• GDP + ATP = GTP + ADP (RHEA:27686)
• a 2’-deoxyribonucleoside 5’-diphosphate + ATP = a 2’-deoxyribonucleoside 5’-triphosphate + ADP (RHEA:44640)

UniProt features (48 total): binding site 22, helix 13, mutagenesis site 5, strand 4, sequence conflict 2, chain 1, active site 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
8QW3	X-RAY DIFFRACTION	1.25
8QVZ	X-RAY DIFFRACTION	1.77
8QW2	X-RAY DIFFRACTION	1.87
8QW1	X-RAY DIFFRACTION	2.1
8QW0	X-RAY DIFFRACTION	2.17
1ZS6	X-RAY DIFFRACTION	2.3
8QVY	X-RAY DIFFRACTION	2.64

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13232-F1	92.67	0.85

Functional residue map

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

Catalytic / active sites (1): 135 (pros-phosphohistidine intermediatee)

Ligand- & substrate-binding residues (22): 111; 111; 111; 122; 122; 129; 129; 129; 129; 132; 29; 132 …

Mutagenesis-validated functional residues (5):

Position	Phenotype
9	lacks phosphatidic acid binding activity; when associated with a-13. decreases nme3 enrichement at the mitochondrial con
13	lacks phosphatidic acid binding activity; when associated with a-9. decreases nme3 enrichement at the mitochondrial cont
40	impairs hexamerization; when associated with d-46. decreases mitochondrial tethering activity; when associated with d-46
46	impairs hexamerization; when associated with d-40. decreases mitochondrial tethering activity; when associated with d-40
135	lacks of nucleoside diphosphate kinase activity. does not affect mitochondrial fusion activity.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-499943	Interconversion of nucleotide di- and triphosphates
R-HSA-1430728	Metabolism
R-HSA-15869	Metabolism of nucleotides

MSigDB gene sets: 233 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_UP, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, GOBP_PYRIMIDINE_NUCLEOSIDE_TRIPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_PYRIMIDINE_NUCLEOTIDE_METABOLIC_PROCESS, RUTELLA_RESPONSE_TO_CSF2RB_AND_IL4_UP, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, GOBP_NUCLEOSIDE_TRIPHOSPHATE_METABOLIC_PROCESS

GO Biological Process (12): GTP biosynthetic process (GO:0006183), UTP biosynthetic process (GO:0006228), dTTP biosynthetic process (GO:0006235), CTP biosynthetic process (GO:0006241), DNA repair (GO:0006281), apoptotic process (GO:0006915), mitochondrial fusion (GO:0008053), nucleoside triphosphate biosynthetic process (GO:0009142), protein hexamerization (GO:0034214), mitochondrial outer membrane fusion (GO:1990626), nervous system development (GO:0007399), nucleotide metabolic process (GO:0009117)

GO Molecular Function (12): nucleoside diphosphate kinase activity (GO:0004550), ATP binding (GO:0005524), GDP binding (GO:0019003), cAMP binding (GO:0030552), ADP binding (GO:0043531), metal ion binding (GO:0046872), phosphatidic acid binding (GO:0070300), mitochondrion-mitochondrion outer membrane tether activity (GO:0160204), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (8): cytoplasm (GO:0005737), mitochondrion (GO:0005739), mitochondrial outer membrane (GO:0005741), cytosol (GO:0005829), ciliary basal body (GO:0036064), cytoskeleton (GO:0005856), membrane (GO:0016020), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Metabolism of nucleotides	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
anion binding	4
cellular anatomical structure	4
adenyl ribonucleotide binding	3
pyrimidine ribonucleoside triphosphate biosynthetic process	2
pyrimidine ribonucleotide biosynthetic process	2
cytoplasm	2
purine ribonucleotide biosynthetic process	1
purine ribonucleoside triphosphate biosynthetic process	1
GTP metabolic process	1
UTP metabolic process	1
deoxyribonucleoside triphosphate biosynthetic process	1
pyrimidine deoxyribonucleoside triphosphate biosynthetic process	1
pyrimidine deoxyribonucleotide biosynthetic process	1
dTTP metabolic process	1
CTP metabolic process	1
DNA metabolic process	1
DNA damage response	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
mitochondrion organization	1
organelle fusion	1
nucleoside triphosphate metabolic process	1
nucleoside phosphate biosynthetic process	1
protein complex oligomerization	1
outer mitochondrial membrane organization	1
mitochondrial fusion	1
system development	1
nucleoside phosphate metabolic process	1
phosphotransferase activity, phosphate group as acceptor	1
nucleobase-containing compound kinase activity	1
purine ribonucleoside triphosphate binding	1
guanyl ribonucleotide binding	1
cyclic nucleotide binding	1
cation binding	1
phospholipid binding	1
membrane-membrane adaptor activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1

Protein interactions and networks

STRING

5610 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NME3	KAT5	Q92993	693
NME3	RP2	O75695	626
NME3	DMTN	Q08495	547
NME3	CKMT1B	P12532	488
NME3	NF1	P21359	449
NME3	A0A087WWV3	A0A087WWV3	446
NME3	LEF1	Q9UJU2	426
NME3	AK5	Q9Y6K8	425
NME3	APRT	P07741	414
NME3	CSF3	P09919	412
NME3	AK9	Q5TCS8	394
NME3	NME1	P15531	382
NME3	DLGAP5	Q15398	376
NME3	DTYMK	P23919	374
NME3	DGUOK	P78532	372

IntAct

98 interactions, top by confidence:

A	B	Type	Score
PRKAG1	PRKAB2	psi-mi:“MI:0914”(association)	0.940
NME1	NME3	psi-mi:“MI:0915”(physical association)	0.800
NME3	NME1	psi-mi:“MI:0915”(physical association)	0.800
NME3	SGTA	psi-mi:“MI:0915”(physical association)	0.780
SGTA	NME3	psi-mi:“MI:0915”(physical association)	0.780
UBQLN1	NME3	psi-mi:“MI:0915”(physical association)	0.720
NME3	UBQLN1	psi-mi:“MI:0915”(physical association)	0.720
IFT27	IFT56	psi-mi:“MI:0914”(association)	0.690
NME3	NME4	psi-mi:“MI:0914”(association)	0.640
SLC17A5	LGALS8	psi-mi:“MI:0914”(association)	0.640
UBQLN1	NME3	psi-mi:“MI:0915”(physical association)	0.560
NME3	UBQLN1	psi-mi:“MI:0915”(physical association)	0.560
NME3	SGTB	psi-mi:“MI:0915”(physical association)	0.560
NME3	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
NME3	DESI1	psi-mi:“MI:0915”(physical association)	0.560
CCT8L2	ACSL4	psi-mi:“MI:0914”(association)	0.530
	NME3	psi-mi:“MI:0915”(physical association)	0.370
NME3		psi-mi:“MI:0915”(physical association)	0.370

BioGRID (152): NME3 (Two-hybrid), SGTA (Two-hybrid), UBQLN1 (Two-hybrid), NME3 (Affinity Capture-MS), SGTA (Two-hybrid), NME3 (Two-hybrid), NME3 (Affinity Capture-MS), NME3 (Affinity Capture-MS), NME3 (Affinity Capture-MS), NME3 (Affinity Capture-MS), NME3 (Affinity Capture-MS), NME3 (Affinity Capture-MS), NME3 (Affinity Capture-MS), NME2 (Affinity Capture-MS), NME2P1 (Affinity Capture-MS)

ESM2 similar proteins: A0A3Q0KJ78, A1SZU8, A2BU01, A2VD68, A5URD5, A6LCB6, A6N0M9, A7I644, A7NFF1, A9AXD6, A9B9E7, A9WFJ8, B0JHT4, B2IX22, B2S4P7, B4FK49, B8G5H0, B8GKL6, B9KGY6, B9LKC5, O81372, O83974, P15266, P39207, P47919, P47921, P48817, P49740, P81766, P93554, Q07661, Q13232, Q1D6I7, Q2JPL4, Q2JVI1, Q39839, Q3M7K5, Q4JAV3, Q56E62, Q5JGR7

Diamond homologs: A0A3Q0KJ78, A2BNH4, A2BU01, A2CDK0, A2VD68, A4J0S4, A5D5U8, A6N0M9, A8G244, B0C4I0, B0JHT4, B0TBN6, B1I1P4, B1WQB7, B2IX22, B4FK49, B8DBZ7, B8FZD1, B8HUM7, B9E6K9, C0ZCD6, C1KWM9, O00746, O29491, O49203, O57535, O60361, O64903, O81372, P08879, P15531, P15532, P19804, P22392, P22887, P27950, P31103, P36010, P39207, P47919

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 76 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Activation of AMPK downstream of NMDARs	5	38.1×	6e-05
Selective autophagy	5	27.9×	1e-04
Post NMDA receptor activation events	5	20.4×	4e-04
Intraflagellar transport	5	20.0×	4e-04
Activation of NMDA receptors and postsynaptic events	5	18.4×	5e-04
Translocation of SLC2A4 (GLUT4) to the plasma membrane	5	15.4×	9e-04
Autophagy	5	14.8×	9e-04
Macroautophagy	5	11.5×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	14
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

401 predictions. Top by Δscore:

Variant	Effect	Δscore
16:1770875:CCTTA:C	donor_loss	1.0000
16:1770876:CTTA:C	donor_loss	1.0000
16:1770877:TTACT:T	donor_loss	1.0000
16:1770878:TA:T	donor_loss	1.0000
16:1770879:A:AC	donor_gain	1.0000
16:1770879:AC:A	donor_loss	1.0000
16:1770880:C:A	donor_loss	1.0000
16:1770880:C:CT	donor_gain	1.0000
16:1770880:CTTG:C	donor_gain	1.0000
16:1770989:CATAC:C	acceptor_gain	1.0000
16:1770991:TAC:T	acceptor_gain	1.0000
16:1770993:CCTG:C	acceptor_gain	1.0000
16:1770996:G:GC	acceptor_gain	1.0000
16:1771064:ACTC:A	donor_loss	1.0000
16:1771066:TCACC:T	donor_loss	1.0000
16:1771068:A:AC	donor_gain	1.0000
16:1771068:A:T	donor_loss	1.0000
16:1771068:AC:A	donor_gain	1.0000
16:1771069:C:CG	donor_gain	1.0000
16:1771069:CC:C	donor_gain	1.0000
16:1771069:CCA:C	donor_gain	1.0000
16:1771315:T:TA	donor_gain	1.0000
16:1771411:C:CC	acceptor_gain	1.0000
16:1770764:TTC:T	acceptor_gain	0.9900
16:1770767:C:CC	acceptor_gain	0.9900
16:1770767:CTGCG:C	acceptor_loss	0.9900
16:1770874:GCCTT:G	donor_loss	0.9900
16:1770990:ATAC:A	acceptor_gain	0.9900
16:1770992:AC:A	acceptor_gain	0.9900
16:1770994:C:CC	acceptor_gain	0.9900

AlphaMissense

1085 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:1770706:G:C	F151L	0.994
16:1770706:G:T	F151L	0.994
16:1770708:A:G	F151L	0.994
16:1770748:G:C	S137R	0.993
16:1770748:G:T	S137R	0.993
16:1770750:T:G	S137R	0.993
16:1771118:G:C	F77L	0.993
16:1771118:G:T	F77L	0.993
16:1771120:A:G	F77L	0.993
16:1771370:C:A	K29N	0.993
16:1771370:C:G	K29N	0.993
16:1770947:C:T	G109E	0.991
16:1770990:A:G	W95R	0.991
16:1770990:A:T	W95R	0.991
16:1770707:A:G	F151S	0.990
16:1770895:G:C	C126W	0.989
16:1770749:C:A	S137I	0.988
16:1770763:G:C	N132K	0.988
16:1770763:G:T	N132K	0.988
16:1770722:T:A	E146V	0.987
16:1770752:C:T	G136D	0.987
16:1770711:A:G	W150R	0.986
16:1770711:A:T	W150R	0.986
16:1770947:C:A	G109V	0.986
16:1771362:C:T	G32D	0.986
16:1770911:A:T	I121N	0.985
16:1770758:A:T	I134N	0.984
16:1770909:G:T	R122S	0.984
16:1770756:G:C	H135D	0.983
16:1770896:C:T	C126Y	0.983

dbSNP variants (sampled 300 via entrez): RS1000080954 (16:1770394 G>A,C), RS1000437713 (16:1770124 C>A,G,T), RS1000745474 (16:1769965 T>C), RS1000988298 (16:1773005 C>G,T), RS1001188624 (16:1770889 C>A,T), RS1002180875 (16:1771576 C>G,T), RS1003213252 (16:1772269 G>A), RS1004283737 (16:1769933 T>G), RS1004356275 (16:1773174 C>A,G,T), RS1004440633 (16:1770095 G>C), RS1005595041 (16:1771837 C>T), RS1005859996 (16:1770442 C>A,T), RS1006459180 (16:1771604 G>A,C,T), RS1007227328 (16:1771867 CAG>C), RS1007434620 (16:1772070 C>T)

Disease associations

OMIM: gene MIM:601817 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
inherited neurodegenerative disorder	Limited	Autosomal recessive

Mondo (1): inherited neurodegenerative disorder (MONDO:0024237)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D020271	Heredodegenerative Disorders, Nervous System	C10.574.500; C16.320.400

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases methylation	3
sodium arsenite	decreases expression	2
Benzo(a)pyrene	decreases expression, increases methylation	2
Estradiol	affects cotreatment, decreases expression	2
Thapsigargin	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	increases expression, affects cotreatment	1
fluorene-9-bisphenol	decreases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
beta-lapachone	decreases expression	1
afimoxifene	decreases response to substance	1
K 7174	decreases expression	1
bisphenol B	increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
bisphenol AF	increases expression	1
Temozolomide	increases expression	1
Sunitinib	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Carbamazepine	affects expression	1
Catechin	affects cotreatment, decreases expression	1
Cisplatin	affects cotreatment, increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	increases O-linked glycosylation, decreases activity	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Menthol	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01498263	Not specified	COMPLETED	Inherited Diseases, Caregiving, and Social Networks