AK9

Summary

AK9 (adenylate kinase 9, HGNC:33814) is a protein-coding gene on chromosome 6q21, encoding Adenylate kinase 9 (Q5TCS8). Broad-specificity nucleoside phosphate kinase involved in cellular nucleotide homeostasis by catalyzing nucleoside-phosphate interconversions.

The protein encoded by this gene catalyzes the interconversion of nucleosides, possessing both nucleoside monophosphate and diphosphate kinase activities. The encoded protein uses these interconversions to maintain nucleoside homeostasis.

Source: NCBI Gene 221264 — RefSeq curated summary.

At a glance

• Gene–disease (curated): postsynaptic congenital myasthenic syndrome (Supportive, GenCC)
• GWAS associations: 4
• Clinical variants (ClinVar): 260 total — 5 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 49
• MANE Select transcript: NM_001145128

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33814
Approved symbol	AK9
Name	adenylate kinase 9
Location	6q21
Locus type	gene with protein product
Status	Approved
Aliases	FLJ42177, FLJ25791, dJ70A9.1, MGC26954
Ensembl gene	ENSG00000155085
Ensembl biotype	protein_coding
OMIM	615358
Entrez	221264

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 10 protein_coding, 1 retained_intron, 1 non_stop_decay

ENST00000285397, ENST00000355283, ENST00000368948, ENST00000424296, ENST00000448084, ENST00000466992, ENST00000470564, ENST00000490722, ENST00000491875, ENST00000524674, ENST00000532976, ENST00000605986

RefSeq mRNA: 4 — MANE Select: NM_001145128 NM_001145128, NM_001329602, NM_001329603, NM_145025

CCDS: CCDS5077, CCDS55048

Canonical transcript exons

ENST00000424296 — 41 exons

Exon	Start	End
ENSE00001282247	109493981	109494095
ENSE00001282255	109495338	109495440
ENSE00001282279	109499044	109499240
ENSE00001423295	109533251	109533470
ENSE00001426214	109542047	109542171
ENSE00001448368	109529011	109529073
ENSE00001505242	109497465	109497563
ENSE00001505243	109497796	109497965
ENSE00001604498	109516430	109516642
ENSE00001605798	109545867	109546127
ENSE00001616652	109515857	109516075
ENSE00001711146	109506327	109506547
ENSE00001754039	109509179	109509380
ENSE00001784899	109514224	109514437
ENSE00001798231	109691147	109691202
ENSE00001801211	109506654	109506800
ENSE00002274535	109492855	109493571
ENSE00003487622	109632923	109633103
ENSE00003497643	109585123	109585237
ENSE00003511518	109614183	109614296
ENSE00003526438	109573442	109573594
ENSE00003529389	109564080	109564280
ENSE00003531258	109644614	109644688
ENSE00003545768	109610365	109610513
ENSE00003554395	109612010	109612093
ENSE00003561199	109619092	109619236
ENSE00003572320	109579550	109579626
ENSE00003593347	109675629	109675756
ENSE00003594600	109585916	109586072
ENSE00003601564	109659228	109659413
ENSE00003622780	109633184	109633323
ENSE00003641111	109564756	109564845
ENSE00003644409	109614385	109614480
ENSE00003655030	109656756	109656884
ENSE00003657069	109672115	109672167
ENSE00003658749	109563597	109563712
ENSE00003670032	109662551	109662663
ENSE00003674255	109674198	109674261
ENSE00003674577	109671919	109672015
ENSE00003676819	109550090	109550302
ENSE00003694262	109641518	109641616

Expression profiles

Bgee: expression breadth ubiquitous, 221 present calls, max score 95.33.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 2.6827 / max 79.2193, expressed in 1096 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
75014	2.3470	1039
75012	0.3088	145
75011	0.0269	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	95.33	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	93.45	gold quality
right uterine tube	UBERON:0001302	91.54	gold quality
bronchial epithelial cell	CL:0002328	91.13	gold quality
bronchus	UBERON:0002185	89.75	gold quality
tendon of biceps brachii	UBERON:0008188	88.44	gold quality
secondary oocyte	CL:0000655	87.55	gold quality
oocyte	CL:0000023	87.49	gold quality
calcaneal tendon	UBERON:0003701	85.96	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.50	gold quality
right testis	UBERON:0004534	85.23	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	84.95	gold quality
tendon	UBERON:0000043	84.91	gold quality
left testis	UBERON:0004533	84.81	gold quality
mucosa of paranasal sinus	UBERON:0005030	84.70	gold quality
testis	UBERON:0000473	84.64	gold quality
medial globus pallidus	UBERON:0002477	84.63	gold quality
oviduct epithelium	UBERON:0004804	83.95	gold quality
ventricular zone	UBERON:0003053	83.42	gold quality
cortical plate	UBERON:0005343	82.68	gold quality
ganglionic eminence	UBERON:0004023	81.97	gold quality
bone marrow cell	CL:0002092	81.43	gold quality
sperm	CL:0000019	80.80	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	80.26	gold quality
epithelium of nasopharynx	UBERON:0001951	80.19	gold quality
nasopharynx	UBERON:0001728	80.18	gold quality
corpus callosum	UBERON:0002336	79.87	gold quality
globus pallidus	UBERON:0001875	79.83	gold quality
pituitary gland	UBERON:0000007	79.36	gold quality
adenohypophysis	UBERON:0002196	79.17	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.04
E-GEOD-124858	no	120.02

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

33 targeting AK9, 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-450A-1-3P	100.00	69.33	1837
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-8076	99.78	68.52	1170
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-29B-2-5P	99.67	68.98	1726
HSA-MIR-6762-3P	99.66	66.94	1188
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-567	99.63	68.57	1219
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-642A-5P	99.51	65.10	1152
HSA-MIR-3612	99.45	66.02	1333
HSA-MIR-650	99.45	65.77	1309
HSA-MIR-297	99.40	69.58	1418
HSA-MIR-3160-5P	99.28	69.07	1938
HSA-MIR-6868-5P	99.06	65.69	1284
HSA-MIR-4742-5P	98.89	68.41	1542

Literature-anchored findings (GeneRIF, showing 4)

• AK2 identified as a novel disease modifier in RASPN-associated limb girdle myasthenia. (PMID:27966543)
• Deficiency in AK9 causes asthenozoospermia and male infertility by destabilising sperm nucleotide homeostasis. (PMID:37713809)
• Integrative analyses of N6-methyladenosine-associated single-nucleotide polymorphisms (m6A-SNPs) identify tumor suppressor gene AK9 in lung cancer. (PMID:38051288)
• A role for mutations in AK9 and other genes affecting ependymal cells in idiopathic normal pressure hydrocephalus. (PMID:38100419)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ak9	ENSDARG00000021913
mus_musculus	Ak9	ENSMUSG00000091415
rattus_norvegicus	Ak9	ENSRNOG00000037688
drosophila_melanogaster	CG9541	FBGN0032083
caenorhabditis_elegans		WBGENE00008746

Paralogs (9): AK2 (ENSG00000004455), AK1 (ENSG00000106992), AK7 (ENSG00000140057), AK3 (ENSG00000147853), AK5 (ENSG00000154027), CMPK1 (ENSG00000162368), AK4 (ENSG00000162433), AK8 (ENSG00000165695), AK4P3 (ENSG00000233381)

Protein

Protein identifiers

Adenylate kinase 9 — Q5TCS8 (reviewed: Q5TCS8)

Alternative names: Adenylate kinase domain-containing protein 1, Adenylate kinase domain-containing protein 2

All UniProt accessions (9): Q5TCS8, A0A075B7F5, E9PPM3, E9PPU7, H0Y8C5, H0YCD1, H7C505, H7C517, J3KP89

UniProt curated annotations — full annotation on UniProt →

Function. Broad-specificity nucleoside phosphate kinase involved in cellular nucleotide homeostasis by catalyzing nucleoside-phosphate interconversions. Similar to other adenylate kinases, preferentially catalyzes the phosphorylation of the nucleoside monophosphate AMP with ATP as phosphate donor to produce ADP. In vitro, can also catalyze the phosphorylation of CMP, dAMP and dCMP and use GTP as an alternate phosphate donor. Moreover, exhibits a diphosphate kinase activity, producing ATP, CTP, GTP, UTP, TTP, dATP, dCTP and dGTP from the corresponding diphosphate substrates with either ATP or GTP as phosphate donors. For this activity shows the following substrate preference CDP > UDP > ADP > TDP.

Subcellular location. Cytoplasm. Nucleus. Cell projection. Cilium. Flagellum.

Disease relevance. Spermatogenic failure 89 (SPGF89) [MIM:620705] An autosomal recessive male infertility disorder due to severely reduced progressive motility of sperm. The disease may be caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the adenylate kinase family.

Isoforms (6)

UniProt ID	Names	Canonical?
Q5TCS8-4	4	yes
Q5TCS8-1	1
Q5TCS8-2	2
Q5TCS8-3	3
Q5TCS8-5	5
Q5TCS8-6	6

RefSeq proteins (4): NP_001138600, NP_001316531, NP_001316532, NP_659462 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000850	Adenylat/UMP-CMP_kin	Family
IPR003593	AAA+_ATPase	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily

Pfam: PF00406, PF13238

Catalyzed reactions (Rhea), 12 shown:

• CMP + ATP = CDP + ADP (RHEA:11600)
• AMP + ATP = 2 ADP (RHEA:12973)
• a ribonucleoside 5’-diphosphate + ATP = a ribonucleoside 5’-triphosphate + ADP (RHEA:18113)
• dAMP + ATP = dADP + ADP (RHEA:23100)
• a ribonucleoside 5’-phosphate + ATP = a ribonucleoside 5’-diphosphate + ADP (RHEA:24036)
• dCMP + ATP = dCDP + ADP (RHEA:25094)
• UDP + ATP = UTP + ADP (RHEA:25098)
• CDP + ATP = CTP + ADP (RHEA:25237)
• dCDP + ATP = dCTP + ADP (RHEA:27678)
• dTDP + ATP = dTTP + ADP (RHEA:27682)
• GDP + ATP = GTP + ADP (RHEA:27686)
• dGDP + ATP = dGTP + ADP (RHEA:27690)

UniProt features (51 total): binding site 13, region of interest 12, splice variant 11, compositionally biased region 5, sequence variant 5, coiled-coil region 2, sequence conflict 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5TCS8-F1	73.70	0.06

Functional residue map

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

Ligand- & substrate-binding residues (13): 40–45; 87–89; 116–119; 229; 1001–1006; 1050–1052; 1079–1082; 1421–1426; 1447; 1470–1472; 1499–1502; 1506 …

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: 191 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, FXR_IR1_Q6, GOBP_NUCLEOSIDE_DIPHOSPHATE_METABOLIC_PROCESS, GCANCTGNY_MYOD_Q6, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_PYRIMIDINE_NUCLEOTIDE_METABOLIC_PROCESS, MYOD_01, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, GOBP_PYRIMIDINE_CONTAINING_COMPOUND_METABOLIC_PROCESS, MYOD_Q6

GO Biological Process (7): UDP biosynthetic process (GO:0006225), CDP biosynthetic process (GO:0046705), nucleobase-containing compound metabolic process (GO:0006139), nucleotide metabolic process (GO:0009117), nucleoside monophosphate metabolic process (GO:0009123), cell projection organization (GO:0030030), nucleoside monophosphate phosphorylation (GO:0046940)

GO Molecular Function (14): AMP kinase activity (GO:0004017), nucleoside diphosphate kinase activity (GO:0004550), ATP binding (GO:0005524), UMP kinase activity (GO:0033862), CMP kinase activity (GO:0036430), dCMP kinase activity (GO:0036431), dAMP kinase activity (GO:0047506), nucleoside monophosphate kinase activity (GO:0050145), nucleotide binding (GO:0000166), kinase activity (GO:0016301), transferase activity (GO:0016740), phosphotransferase activity, phosphate group as acceptor (GO:0016776), ATP hydrolysis activity (GO:0016887), nucleobase-containing compound kinase activity (GO:0019205)

GO Cellular Component (11): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), microtubule cytoskeleton (GO:0015630), motile cilium (GO:0031514), nuclear membrane (GO:0031965), sperm glycocalyx (GO:0120238), cytoskeleton (GO:0005856), cilium (GO:0005929), 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
cellular anatomical structure	4
nucleoside monophosphate kinase activity	3
pyrimidine ribonucleoside diphosphate biosynthetic process	2
pyrimidine ribonucleotide biosynthetic process	2
nucleoside phosphate metabolic process	2
phosphotransferase activity, phosphate group as acceptor	2
nucleobase-containing compound kinase activity	2
deoxynucleoside phosphate kinase activity, ATP as phosphate donor	2
transferase activity, transferring phosphorus-containing groups	2
UDP metabolic process	1
CDP metabolic process	1
primary metabolic process	1
cellular component organization	1
nucleoside monophosphate metabolic process	1
nucleotide biosynthetic process	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
catalytic activity	1
ribonucleoside triphosphate phosphatase activity	1
ATP-dependent activity	1
kinase activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
cytoskeleton	1
cilium	1
nucleus	1
nuclear envelope	1
organelle membrane	1
glycocalyx	1
intracellular membraneless organelle	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1

Protein interactions and networks

STRING

2939 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AK9	AK6	Q9Y3D8	593
AK9	CIMIP5	Q96LR7	582
AK9	AK8	Q96MA6	566
AK9	TCTA	P57738	504
AK9	SLC33A2	Q96ES6	490
AK9	AK7	Q96M32	480
AK9	ABCG8	Q9H221	456
AK9	AK3	Q9UIJ7	437
AK9	OR6C70	A6NIJ9	436
AK9	CFAP210	Q0VFZ6	432
AK9	AK5	Q9Y6K8	431
AK9	NME6	O75414	426
AK9	OR2L3	Q8NG85	419
AK9	DTYMK	P23919	414
AK9	ITPA	Q9BY32	412

IntAct

10 interactions, top by confidence:

A	B	Type	Score
	CD5L	psi-mi:“MI:0915”(physical association)	0.400
	LECT2	psi-mi:“MI:0915”(physical association)	0.400
CUL4A	HAX1	psi-mi:“MI:0914”(association)	0.350
ATG16L1		psi-mi:“MI:0914”(association)	0.350
AK9	MYO9A	psi-mi:“MI:0914”(association)	0.350
INSR	RIMOC1	psi-mi:“MI:0914”(association)	0.350
	AK9	psi-mi:“MI:0915”(physical association)	0.000
AK9	PEA15	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (28): HSP90B1 (Co-fractionation), RHOA (Affinity Capture-MS), LRRC23 (Affinity Capture-MS), EXOG (Affinity Capture-MS), C5orf34 (Affinity Capture-MS), HDAC3 (Affinity Capture-MS), TAF2 (Affinity Capture-MS), MYO9A (Affinity Capture-MS), PRIM1 (Affinity Capture-MS), AK9 (Two-hybrid), AK9 (Affinity Capture-MS), RHOA (Affinity Capture-MS), TAF2 (Affinity Capture-MS), EXOG (Affinity Capture-MS), C5orf34 (Affinity Capture-MS)

ESM2 similar proteins: A1L1R5, A5PKL1, A8E7C5, A8KBE0, B2RC85, B4F7L9, B4GQJ7, B5DHW4, B7FF07, B7FF08, B7FF12, D3YVL2, E7FDW2, E9PYQ0, G3UYQ4, G5EFD2, O00522, P0C881, P27671, P59111, Q08CH7, Q12923, Q14693, Q1JPG1, Q5TCS8, Q5VZ89, Q640I9, Q66HB5, Q68FF0, Q6DTM3, Q6NSI8, Q6S5J6, Q6TNJ1, Q6ZT98, Q8BRB7, Q8CDA1, Q8CDM1, Q8CIS0, Q8K3E5, Q8N157

Diamond homologs: A0A3Q0KGQ7, A0A4X1T4U3, A0K9X1, A1JNB1, A1STI3, A1T4T2, A1UBR9, A1V117, A2S516, A3M3G1, A3MN48, A3N6K4, A3NS87, A3PVF5, A3QF48, A4JH80, A4TPA4, A4XLR0, A5CU93, A5N4R8, A6L0Z9, A6LD69, A6T5N7, A7FL86, A8AJW9, A9R0Q7, B0RB59, B0TP07, B0V9Q9, B0VSA9, B1AIP0, B1JHN1, B1JXF8, B1MGB3, B2HVT0, B2K6Z6, B4E9G1, B4F1Q2, B4SWY1, B4T9I1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	3
Uncertain significance	197
Likely benign	15
Benign	14

Top pathogenic / likely-pathogenic (8)

Variant ID	HGVS	Classification
2692351	NM_001145128.3(AK9):c.4872_4875dup (p.Cys1626fs)	Pathogenic
2692352	NM_001145128.3(AK9):c.2005dup (p.Cys669fs)	Pathogenic
2692354	NM_001145128.3(AK9):c.2444C>T (p.Pro815Leu)	Pathogenic
3062884	GRCh37/hg19 6q21(chr6:109925900-110080533)x1	Pathogenic
3246049	NC_000006.11:g.(?109765394)(110053910_?)del	Pathogenic
148323	GRCh38/hg38 6q21(chr6:109612069-109749371)x1	Likely pathogenic
4845845	NM_001145128.3(AK9):c.3225+1G>A	Likely pathogenic
4849301	NM_001145128.3(AK9):c.2747_2751+1dupAAGAGG	Likely pathogenic

SpliceAI

7310 predictions. Top by Δscore:

Variant	Effect	Δscore
6:109506796:CAACA:C	acceptor_gain	1.0000
6:109506799:CA:C	acceptor_gain	1.0000
6:109506801:C:CC	acceptor_gain	1.0000
6:109516455:T:C	donor_gain	1.0000
6:109516639:CATT:C	acceptor_gain	1.0000
6:109516641:TT:T	acceptor_gain	1.0000
6:109533249:AC:A	donor_gain	1.0000
6:109533250:CC:C	donor_gain	1.0000
6:109542083:A:AC	donor_gain	1.0000
6:109542084:C:CC	donor_gain	1.0000
6:109542086:T:TA	donor_gain	1.0000
6:109542169:AAGC:A	acceptor_loss	1.0000
6:109542172:C:CC	acceptor_gain	1.0000
6:109542172:C:CG	acceptor_loss	1.0000
6:109545861:TACTA:T	donor_loss	1.0000
6:109545864:TACCT:T	donor_loss	1.0000
6:109545865:ACCT:A	donor_loss	1.0000
6:109545866:C:CT	donor_loss	1.0000
6:109545866:CCTG:C	donor_gain	1.0000
6:109545886:T:TA	donor_gain	1.0000
6:109546728:T:C	acceptor_gain	1.0000
6:109546728:T:TC	acceptor_gain	1.0000
6:109550085:CTCA:C	donor_loss	1.0000
6:109550086:TCA:T	donor_loss	1.0000
6:109550087:CACC:C	donor_loss	1.0000
6:109550088:A:AC	donor_gain	1.0000
6:109550089:C:CC	donor_gain	1.0000
6:109550089:CCTT:C	donor_gain	1.0000
6:109563601:T:A	donor_gain	1.0000
6:109563607:T:TA	donor_gain	1.0000

AlphaMissense

12702 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:109515884:G:C	S1346R	0.997
6:109515884:G:T	S1346R	0.997
6:109515886:T:G	S1346R	0.997
6:109497961:A:G	F1684S	0.995
6:109550248:A:G	C936R	0.995
6:109497960:G:C	F1684L	0.994
6:109497960:G:T	F1684L	0.994
6:109497962:A:G	F1684L	0.994
6:109514325:A:G	F1393S	0.994
6:109515959:G:C	S1321R	0.994
6:109515959:G:T	S1321R	0.994
6:109515961:T:G	S1321R	0.994
6:109533459:A:G	F1121S	0.994
6:109659332:A:G	W176R	0.994
6:109659332:A:T	W176R	0.994
6:109586021:A:G	W632R	0.993
6:109586021:A:T	W632R	0.993
6:109619146:C:G	A449P	0.993
6:109633269:A:G	W330R	0.993
6:109633269:A:T	W330R	0.993
6:109493986:A:G	L1843P	0.992
6:109499086:G:C	F1668L	0.992
6:109499086:G:T	F1668L	0.992
6:109499088:A:G	F1668L	0.992
6:109542066:A:G	W1111R	0.992
6:109542066:A:T	W1111R	0.992
6:109550136:A:G	F973S	0.992
6:109619158:C:G	A445P	0.992
6:109633254:A:G	W335R	0.992
6:109633254:A:T	W335R	0.992

dbSNP variants (sampled 300 via entrez): RS1000004007 (6:109664932 C>T), RS1000025669 (6:109531141 A>G), RS1000046699 (6:109677310 C>T), RS1000051448 (6:109586380 C>T), RS1000086521 (6:109637186 A>G), RS1000100001 (6:109664726 A>G), RS1000105082 (6:109496665 T>C), RS1000124940 (6:109581890 ACT>A), RS1000126214 (6:109559577 T>C), RS1000126981 (6:109536777 C>G), RS1000159011 (6:109642097 C>T), RS1000190194 (6:109657708 C>A), RS1000200590 (6:109598989 G>A,C,T), RS1000215778 (6:109676008 A>C), RS1000244795 (6:109562595 G>A)

Disease associations

OMIM: gene MIM:615358 | disease phenotypes: MIM:620705

GenCC curated gene-disease

Disease	Classification	Inheritance
postsynaptic congenital myasthenic syndrome	Supportive	Autosomal recessive

Mondo (3): spermatogenic failure 89 (MONDO:0958206), Charcot-Marie-Tooth disease type 4 (MONDO:0018995), postsynaptic congenital myasthenic syndrome (MONDO:0020344)

Orphanet (1): Charcot-Marie-Tooth disease type 4 (Orphanet:64749)

HPO phenotypes

49 total (30 of 49 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000218	High palate
HP:0000496	Abnormality of eye movement
HP:0000508	Ptosis
HP:0000597	Ophthalmoparesis
HP:0000651	Diplopia
HP:0000798	Oligozoospermia
HP:0000961	Cyanosis
HP:0001315	Reduced tendon reflexes
HP:0001324	Muscle weakness
HP:0001446	Abnormality of the musculature of the upper limbs
HP:0002091	Restrictive ventilatory defect
HP:0002194	Delayed gross motor development
HP:0002329	Drowsiness
HP:0002650	Scoliosis
HP:0002792	Reduced vital capacity
HP:0002875	Exertional dyspnea
HP:0002878	Respiratory failure
HP:0003202	Skeletal muscle atrophy
HP:0003251	Male infertility
HP:0003388	Easy fatigability
HP:0003402	Decreased miniature endplate potentials
HP:0003403	EMG: decremental response of compound muscle action potential to repetitive nerve stimulation
HP:0003443	Decreased size of nerve terminals
HP:0003458	EMG: myopathic abnormalities
HP:0003484	Upper limb muscle weakness
HP:0003547	Shoulder girdle muscle weakness
HP:0003722	Neck flexor weakness
HP:0003803	Type 1 muscle fiber predominance
HP:0005659	Thoracic kyphoscoliosis

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST000465_2	Response to hepatitis C treatment	7.000000e-06
GCST004749_106	Lung cancer in ever smokers	6.000000e-06
GCST006427_1	Depression in smokers	4.000000e-07
GCST90020028_540	Hip circumference adjusted for BMI	2.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression, decreases methylation	8
sodium arsenite	decreases expression, increases expression	2
Cyclosporine	increases expression	2
GSK-J4	decreases expression	1
FR900359	affects phosphorylation	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
beta-lapachone	decreases expression	1
sulforaphane	increases expression	1
zinc chromate	increases expression, increases abundance	1
ferrous chloride	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	increases abundance, increases expression	1
perfluorooctane sulfonic acid	increases expression	1
tanespimycin	affects cotreatment, decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	increases expression, affects cotreatment	1
VER 155008	affects cotreatment, decreases expression	1
2,3,5-trichloro-6-phenyl-(1,4)benzoquinone	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Vorinostat	affects cotreatment, increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Estradiol	affects cotreatment, decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Methyl Methanesulfonate	increases expression	1
Nickel	decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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