AMDHD2

Summary

AMDHD2 (amidohydrolase domain containing 2, HGNC:24262) is a protein-coding gene on chromosome 16p13.3, encoding N-acetylglucosamine-6-phosphate deacetylase (Q9Y303). Hydrolyzes the N-glycolyl group from N-glycolylglucosamine 6-phosphate (GlcNGc-6-P) in the N-glycolylneuraminic acid (Neu5Gc) degradation pathway.

Enables N-acetylglucosamine-6-phosphate deacetylase activity. Involved in negative regulation of UDP-N-acetylglucosamine biosynthetic process. Located in nucleus.

Source: NCBI Gene 51005 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• Clinical variants (ClinVar): 120 total — 2 pathogenic, 4 likely-pathogenic
• GTEx eGene: eQTL in 31 tissues, sQTL in 16 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.87 (unconstrained)
• MANE Select transcript: NM_001330449
• Notable: 120 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24262
Approved symbol	AMDHD2
Name	amidohydrolase domain containing 2
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Aliases	CGI-14
Ensembl gene	ENSG00000162066
Ensembl biotype	protein_coding
OMIM	620864
Entrez	51005

Gene structure

Transcript identifiers

Ensembl transcripts: 48 — 20 nonsense_mediated_decay, 18 protein_coding, 9 retained_intron, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000293971

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 10, TSL 3: 1, TSL 4: 1, TSL 5: 4

ENST00000293971, ENST00000302956, ENST00000413459, ENST00000561487, ENST00000563145, ENST00000563444, ENST00000563453, ENST00000563556, ENST00000563633, ENST00000565570, ENST00000565963, ENST00000566706, ENST00000566947, ENST00000567475, ENST00000568263, ENST00000569219, ENST00000569879, ENST00000570028, ENST00000648227, ENST00000872243, ENST00000872244, ENST00000872245, ENST00000872246, ENST00000872247, ENST00000915809, ENST00000989803, ENST00000989804, ENST00000989805, ENST00000989806, ENST00000989807, ENST00000989808, ENST00001047233, ENST00001047234, ENST00001047235, ENST00001047236, ENST00001047237, ENST00001047238, ENST00001047239, ENST00001047240, ENST00001047241, ENST00001066241, ENST00001066242, ENST00001066243, ENST00001066244, ENST00001066245, ENST00001066246, ENST00001066247, ENST00001135628

RefSeq mRNA: 4 — MANE Select: NM_001330449 NM_001145815, NM_001330449, NM_001410943, NM_015944

CCDS: CCDS10471, CCDS53984, CCDS81936, CCDS92088

Canonical transcript exons

ENST00000293971 — 11 exons

Exon	Start	End
ENSE00001234307	2529475	2531417
ENSE00003496199	2528452	2528559
ENSE00003505260	2528650	2528718
ENSE00003514246	2528994	2529095
ENSE00003527301	2520984	2521123
ENSE00003541132	2528060	2528148
ENSE00003563063	2520769	2520905
ENSE00003565655	2527561	2527615
ENSE00003590669	2528236	2528380
ENSE00003605028	2527773	2527985
ENSE00003905479	2520371	2520541

Expression profiles

Bgee: expression breadth ubiquitous, 173 present calls, max score 94.46.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.6778 / max 148.7481, expressed in 1805 samples.

Highest expression (Bgee): testis, adrenal gland cortex, adrenal gland, hemisphere of cerebellum, spleen.

Genetic regulation across tissues (GTEx eQTL / sQTL)

AMDHD2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 31 tissues and its splicing (sQTL) in 16 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 47 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Thyroid	eqtl	1.4e-17	-0.41	16:2520290:GTCACGTGGGCTGGCTCGA:G
Pancreas	eqtl	5.2e-17	-0.56	16:2520290:GTCACGTGGGCTGGCTCGA:G
Adipose Subcutaneous	sqtl	1.8e-15	+1.79	16:2521330:C:T
Esophagus Mucosa	eqtl	4.5e-13	-0.41	16:2520290:GTCACGTGGGCTGGCTCGA:G
Artery Tibial	eqtl	3.4e-10	-0.32	16:2520290:GTCACGTGGGCTGGCTCGA:G
Nerve Tibial	eqtl	1.2e-09	-0.31	16:2487169:C:T
Esophagus Muscularis	sqtl	1.8e-09	+1.64	16:2528130:C:G
Muscle Skeletal	eqtl	4.1e-09	+0.46	16:2541127:T:C
Adrenal Gland	sqtl	9.9e-09	+1.79	16:2506600:G:T
Cells Cultured fibroblasts	eqtl	6.4e-07	-0.18	16:2520290:GTCACGTGGGCTGGCTCGA:G
Spleen	sqtl	7.6e-07	+1.41	16:2492635:C:T
Stomach	eqtl	1.0e-06	-0.38	16:2520290:GTCACGTGGGCTGGCTCGA:G
Thyroid	sqtl	1.1e-06	+1.57	16:2527012:G:A
Adipose Subcutaneous	eqtl	1.6e-06	-0.20	16:2520290:GTCACGTGGGCTGGCTCGA:G
Artery Tibial	sqtl	2.0e-06	+1.53	16:2598069:C:T
Lung	eqtl	6.6e-06	-0.15	16:2598917:C:T
Testis	eqtl	8.7e-06	-0.16	16:2487169:C:T
Colon Sigmoid	eqtl	1.0e-05	-0.30	16:2520290:GTCACGTGGGCTGGCTCGA:G
Artery Aorta	sqtl	1.4e-05	+1.78	16:2477821:G:A
Brain Caudate basal ganglia	eqtl	1.8e-05	-0.39	16:2520290:GTCACGTGGGCTGGCTCGA:G

FANTOM5 promoters

3 alternative TSS:

Promoter ID	TPM avg	Samples expressed
152246	11.5811	1803
152247	0.9614	604
152248	0.1353	52

Top tissues by expression

showing 100 of 277 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	94.46	gold quality
right testis	UBERON:0004534	93.61	gold quality
testis	UBERON:0000473	91.28	gold quality
right adrenal gland cortex	UBERON:0035827	91.06	gold quality
right adrenal gland	UBERON:0001233	90.81	gold quality
right hemisphere of cerebellum	UBERON:0014890	90.36	gold quality
spleen	UBERON:0002106	90.08	gold quality
left adrenal gland	UBERON:0001234	90.02	gold quality
right uterine tube	UBERON:0001302	90.02	gold quality
left adrenal gland cortex	UBERON:0035825	89.90	gold quality
small intestine Peyer’s patch	UBERON:0003454	89.82	gold quality
cerebellar hemisphere	UBERON:0002245	89.49	gold quality
cerebellar cortex	UBERON:0002129	89.41	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.09	gold quality
adrenal cortex	UBERON:0001235	88.57	gold quality
granulocyte	CL:0000094	88.48	gold quality
right lobe of thyroid gland	UBERON:0001119	88.44	gold quality
right frontal lobe	UBERON:0002810	88.15	gold quality
stromal cell of endometrium	CL:0002255	88.12	gold quality
metanephros cortex	UBERON:0010533	87.83	gold quality
transverse colon	UBERON:0001157	87.59	gold quality
left lobe of thyroid gland	UBERON:0001120	87.46	gold quality
minor salivary gland	UBERON:0001830	87.40	gold quality
adrenal gland	UBERON:0002369	87.35	gold quality
small intestine	UBERON:0002108	87.21	gold quality
cerebellum	UBERON:0002037	87.12	gold quality
apex of heart	UBERON:0002098	86.78	gold quality
skin of leg	UBERON:0001511	86.57	gold quality
ectocervix	UBERON:0012249	86.57	gold quality
mucosa of transverse colon	UBERON:0004991	86.52	gold quality
mucosa of stomach	UBERON:0001199	86.46	gold quality
muscle layer of sigmoid colon	UBERON:0035805	86.45	gold quality
thyroid gland	UBERON:0002046	86.19	gold quality
blood	UBERON:0000178	86.13	gold quality
upper lobe of left lung	UBERON:0008952	86.07	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	86.03	gold quality
right lobe of liver	UBERON:0001114	86.01	gold quality
right ovary	UBERON:0002118	86.01	gold quality
omental fat pad	UBERON:0010414	86.01	gold quality
peritoneum	UBERON:0002358	85.95	gold quality
skin of abdomen	UBERON:0001416	85.90	gold quality
anterior cingulate cortex	UBERON:0009835	85.82	gold quality
prefrontal cortex	UBERON:0000451	85.75	gold quality
endocervix	UBERON:0000458	85.70	gold quality
left coronary artery	UBERON:0001626	85.70	gold quality
cingulate cortex	UBERON:0003027	85.68	gold quality
right coronary artery	UBERON:0001625	85.60	gold quality
body of stomach	UBERON:0001161	85.52	gold quality
left uterine tube	UBERON:0001303	85.47	gold quality
body of uterus	UBERON:0009853	85.42	gold quality
lower esophagus	UBERON:0013473	85.38	gold quality
lower esophagus muscularis layer	UBERON:0035833	85.38	gold quality
adipose tissue of abdominal region	UBERON:0007808	85.21	gold quality
adenohypophysis	UBERON:0002196	85.11	gold quality
mouth mucosa	UBERON:0003729	84.99	gold quality
sural nerve	UBERON:0015488	84.85	gold quality
coronary artery	UBERON:0001621	84.77	gold quality
pituitary gland	UBERON:0000007	84.56	gold quality
esophagus	UBERON:0001043	84.45	gold quality
saliva-secreting gland	UBERON:0001044	84.42	gold quality
gall bladder	UBERON:0002110	84.33	gold quality
lower esophagus mucosa	UBERON:0035834	84.30	gold quality
left ovary	UBERON:0002119	84.28	gold quality
subcutaneous adipose tissue	UBERON:0002190	84.19	gold quality
upper lobe of lung	UBERON:0008948	84.05	gold quality
esophagus mucosa	UBERON:0002469	84.04	gold quality
Brodmann (1909) area 9	UBERON:0013540	84.01	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	83.74	gold quality
thoracic aorta	UBERON:0001515	83.68	gold quality
tibial nerve	UBERON:0001323	83.65	gold quality
ascending aorta	UBERON:0001496	83.60	gold quality
descending thoracic aorta	UBERON:0002345	83.54	gold quality
nucleus accumbens	UBERON:0001882	83.33	gold quality
hindlimb stylopod muscle	UBERON:0004252	83.22	gold quality
aorta	UBERON:0000947	83.15	gold quality
lymph node	UBERON:0000029	83.04	gold quality
neocortex	UBERON:0001950	83.03	gold quality
zone of skin	UBERON:0000014	82.94	gold quality
frontal cortex	UBERON:0001870	82.93	gold quality
popliteal artery	UBERON:0002250	82.90	gold quality
tibial artery	UBERON:0007610	82.89	gold quality
monocyte	CL:0000576	82.82	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	82.77	gold quality
stomach	UBERON:0000945	82.74	gold quality
intestine	UBERON:0000160	82.70	gold quality
right lung	UBERON:0002167	82.59	gold quality
leukocyte	CL:0000738	82.56	gold quality
mononuclear cell	CL:0000842	82.52	gold quality
colon	UBERON:0001155	82.44	gold quality
caudate nucleus	UBERON:0001873	82.40	gold quality
large intestine	UBERON:0000059	81.73	gold quality
spinal cord	UBERON:0002240	81.71	gold quality
putamen	UBERON:0001874	81.66	gold quality
fundus of stomach	UBERON:0001160	81.62	gold quality
body of pancreas	UBERON:0001150	81.54	gold quality
ventricular zone	UBERON:0003053	81.36	gold quality
adipose tissue	UBERON:0001013	81.35	gold quality
right atrium auricular region	UBERON:0006631	81.26	gold quality
anatomical system	UBERON:0000467	81.17	gold quality
cortical plate	UBERON:0005343	81.11	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.27

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 77 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Cerebral cortex	tissue	58.4	not detected
Somatosensory cortex	tissue	58.4
Motor cortex	tissue	57.1
Thalamus	tissue	56.5
Pons	tissue	55.5
Hippocampal formation	tissue	55.5
Retrosplenial and cingulate cortex	tissue	53.2
Prefrontal cortex	tissue	52.9
Occipital cortex	tissue	52.2
Entorhinal cortex	tissue	51.8
Superior colliculi	tissue	51.5
Temporal cortex	tissue	51.5
Retrosplenial cortex	tissue	50.6
Putamen	tissue	50.5
Midbrain	tissue	50.3
Basal ganglia	tissue	49.4	not detected
Insular cortex	tissue	49.0
Substantia nigra	tissue	48.9
Hypothalamus	tissue	47.2
Ventral forebrain	tissue	46.1
Septum	tissue	45.9
Amygdala	tissue	45.2
Medulla oblongata	tissue	45.1
Spinal cord	tissue	43.3
Periaqueductal gray	tissue	39.8
Cerebellum	tissue	37.5	not detected
Olfactory bulb	tissue	37.2
Corpus callosum	tissue	34.7
Frontal cortex	tissue	12.0
Spleen	tissue	9.8	low
Small intestine	tissue	9.2	low
Caudate putamen	tissue	9.1
Duodenum	tissue	8.5	medium
Pituitary gland	tissue	7.8
Vagina	tissue	7.8	not detected
Lymph node	tissue	7.4	not detected
Salivary gland	tissue	6.9	not detected
Choroid plexus	tissue	6.9
Skin 1	tissue	6.7	not detected
Locus coeruleus	tissue	6.6
Hippocampus	tissue	6.4	not detected
Kidney	tissue	6.3	medium
Adrenal gland	tissue	5.9	high
Adipose tissue	tissue	5.8	not detected
Nucleus accumbens	tissue	5.3
Appendix	tissue	5.3	not detected
Bone marrow	tissue	5.2	medium
Testis	tissue	4.9	medium
Stomach 1	tissue	4.8	medium
Skeletal muscle	tissue	4.5	low
Placenta	tissue	4.3	low
Gallbladder	tissue	4.1	low
Liver	tissue	4.0	not detected
Thymus	tissue	3.5
Postcentral gyrus	tissue	3.5
Endometrium 1	tissue	3.4	not detected
Lung	tissue	3.4	low
Ovary	tissue	3.2	low
Pancreas	tissue	3.2	not detected
Seminal vesicle	tissue	3.0	not detected

Brain sub-regions (HPA Brain Atlas): detected in 190; highest nTPM — Ventral hippocampus (55.5), Dorsal hippocampus (55.0), Subiculum (52.0), Ventral spinal cord (43.3), Dorsal spinal cord (40.1).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting AMDHD2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

1 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4308	97.56	67.13	1385

Functional genomics

gnomAD constraint: pLI 2.16e-05, LOEUF 0.868, missense Z 0.393 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000293971 — one region, missense o/e 0.92.

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	amdhd2	ENSDARG00000100376
mus_musculus	Amdhd2	ENSMUSG00000036820
rattus_norvegicus	Amdhd2	ENSRNOG00000006460
drosophila_melanogaster	CG17065	FBGN0031099
caenorhabditis_elegans		WBGENE00010308

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:2443978) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 4 distinct phenotype terms.

Mouse phenotype (MP)	Records
enhanced contextual conditioning behavior	1
prenatal lethality, complete penetrance	1
preweaning lethality, complete penetrance	1
increased freezing behavior	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Escherichia coli K-12	P0AF18	100.0%	Diamond
Escherichia coli O157:H7	P0AF19	100.0%	Diamond
Bos taurus	A7MBC0	92.2%	Diamond
Vibrio cholerae O1 biovar El Tor str. N16961	O32445	62.0%	Diamond
Haemophilus influenzae Rd KW20	P44537	55.3%	Diamond
Vibrio furnissii	P96166	53.0%	Diamond
Bacillus subtilis subsp. subtilis str. 168	O34450	43.6%	Diamond
Lysinibacillus sphaericus	Q84F86	43.6%	Diamond
Shewanella sp. ANA-3	A0KYQ5	36.6%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
PDPK1	protein-coding	5170
ATP6V0C	protein-coding	527
CEMP1	protein-coding	752014
NTN3	protein-coding	4917
TBC1D24	protein-coding	57465
TEDC2-AS1	ncRNA	729652
TEDC2	protein-coding	80178
MIR3178	ncRNA	100422974
FLJ42627	ncRNA	645644

Protein

Protein identifiers

N-acetylglucosamine-6-phosphate deacetylase — Q9Y303 (reviewed: Q9Y303)

Alternative names: Amidohydrolase domain-containing protein 2

All UniProt accessions (7): A0A3B3IU33, Q9Y303, H3BSD5, H3BSV9, H3BT49, H3BTE3, H3BTZ6

UniProt curated annotations — full annotation on UniProt →

Function. Hydrolyzes the N-glycolyl group from N-glycolylglucosamine 6-phosphate (GlcNGc-6-P) in the N-glycolylneuraminic acid (Neu5Gc) degradation pathway. Although human is not able to catalyze formation of Neu5Gc due to the inactive CMAHP enzyme, Neu5Gc is present in food and must be degraded.

Cofactor. Binds 1 divalent metal cation per subunit.

Pathway. Amino-sugar metabolism; N-acetylneuraminate degradation.

Similarity. Belongs to the metallo-dependent hydrolases superfamily. NagA family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9Y303-1	1	yes
Q9Y303-2	2
Q9Y303-3	3

RefSeq proteins (4): NP_001139287, NP_001317378, NP_001397872, NP_057028 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003764	GlcNAc_6-P_deAcase	Family
IPR006680	Amidohydro-rel	Domain
IPR011059	Metal-dep_hydrolase_composite	Homologous_superfamily
IPR032466	Metal_Hydrolase	Homologous_superfamily

Pfam: PF01979

Catalyzed reactions (Rhea)

• N-acetyl-D-glucosamine 6-phosphate + H2O = D-glucosamine 6-phosphate + acetate (RHEA:22936)

UniProt features (66 total): strand 26, helix 17, binding site 8, sequence conflict 5, turn 5, splice variant 2, chain 1, active site 1, sequence variant 1

Structure

Experimental structures (PDB)

2 structures by resolution:

PDB	Title	Method	Resolution (Å)
7NUU	Crystal structure of human AMDHD2 in complex with Zn	X-RAY DIFFRACTION	1.84
7NUT	Crystal structure of human AMDHD2 in complex with Zn and GlcN6P	X-RAY DIFFRACTION	1.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y303-F1	94.49	0.87

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Hydrolases, Metabolic proteins, Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol; nucleoli

Antibody reliability (HPA): IH enhanced · IF approved

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)

Position	Role
294	proton donor/acceptor

Ligand- & substrate-binding residues (8)

Position	Role
143	a divalent metal cation
154–155	substrate
211	a divalent metal cation
232	a divalent metal cation
235–236	substrate
243	substrate
269–272	substrate
328–330	substrate

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 6; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

6 pathways:

ID	Pathway	Evidence
R-HSA-446210	Synthesis of UDP-N-acetyl-glucosamine	curated
R-HSA-446203	Asparagine N-linked glycosylation	—
R-HSA-446193	Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein	—
R-HSA-392499	Metabolism of proteins	—
R-HSA-597592	Post-translational protein modification	—
R-HSA-446219	Synthesis of substrates in N-glycan biosythesis	—

MSigDB gene sets: 134 (showing top): RNGTGGGC_UNKNOWN, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_AMINO_SUGAR_BIOSYNTHETIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, CHANDRAN_METASTASIS_DN, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_AMIDE_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, GOBP_ORGANIC_ACID_CATABOLIC_PROCESS, USF_01, GOBP_NEGATIVE_REGULATION_OF_PHOSPHORUS_METABOLIC_PROCESS, GOBP_AMINO_SUGAR_CATABOLIC_PROCESS

GO Biological Process (5): N-acetylglucosamine catabolic process (GO:0006046), UDP-N-acetylglucosamine biosynthetic process (GO:0006048), N-acetylneuraminate catabolic process (GO:0019262), negative regulation of UDP-N-acetylglucosamine biosynthetic process (GO:0106279), N-acetylglucosamine metabolic process (GO:0006044)

GO Molecular Function (5): N-acetylglucosamine-6-phosphate deacetylase activity (GO:0008448), metal ion binding (GO:0046872), protein binding (GO:0005515), hydrolase activity (GO:0016787), hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds (GO:0016810)

GO Cellular Component (2): nucleus (GO:0005634), cytosol (GO:0005829)

Reactome top-level categories

5 top-level categories:

Category	Pathways
Synthesis of substrates in N-glycan biosythesis	1
Asparagine N-linked glycosylation	1
Post-translational protein modification	1
Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein	1
Metabolism of proteins	1

GO top-level categories

24 GO namespaces:

Category	Terms
N-acetylglucosamine metabolic process	1
glucosamine-containing compound catabolic process	1
UDP-N-acetylglucosamine metabolic process	1
nucleotide-sugar biosynthetic process	1
amino sugar biosynthetic process	1
N-acetylneuraminate metabolic process	1
amino sugar catabolic process	1
carboxylic acid catabolic process	1
UDP-N-acetylglucosamine biosynthetic process	1
negative regulation of biosynthetic process	1
negative regulation of phosphorus metabolic process	1
negative regulation of nucleobase-containing compound metabolic process	1
negative regulation of small molecule metabolic process	1
regulation of UDP-N-acetylglucosamine biosynthetic process	1
amino sugar metabolic process	1
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides	1
deacetylase activity	1
cation binding	1
binding	1
catalytic activity	1
hydrolase activity	1
intracellular membrane-bounded organelle	1
cytoplasm	1
cellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 3 of 12 annotations. The rest are phylogenetic / computational / electronic (IEA).

3 experimentally-supported GO terms:

GO term	NS	Evidence
negative regulation of UDP-N-acetylglucosamine biosynthetic process	BP	direct assay
nucleus	CC	high-throughput assay
N-acetylglucosamine-6-phosphate deacetylase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 574 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AMDHD2	GNPDA1	P46926	806
AMDHD2	GNPDA2	Q8TDQ7	780
AMDHD2	LITAFD	A0A1B0GVX0	551
AMDHD2	GFPT2	O94808	509
AMDHD2	NAGA	P17050	499
AMDHD2	OR6N1	Q8NGY5	499
AMDHD2	PGM3	O95394	482
AMDHD2	GFPT1	Q06210	476
AMDHD2	NAGK	Q9UJ70	476
AMDHD2	OR6N2	Q8NGY6	469
AMDHD2	GALM	Q96C23	448
AMDHD2	ZMYM6	O95789	432
AMDHD2	CARHSP1	Q9Y2V2	428
AMDHD2	GNPNAT1	Q96EK6	395
AMDHD2	ZBTB25	P24278	394

IntAct

Human interaction partners of AMDHD2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

2 partners by confidence:

Partner	Interaction type	MIscore	Records
GNPDA2	physical association	0.800	4
TRIP13	physical association	0.560	3

BioGRID (18 interactions; top human partners by supporting records): GNPDA2 (Two-hybrid; 5 records), GNPDA1 (Affinity Capture-MS; 4 records), TRIP13 (Two-hybrid; 2 records), MARCKS (Co-fractionation), NUDT21 (Affinity Capture-RNA), PARK2 (Affinity Capture-MS), PKM (Co-fractionation), SPPL3 (Positive Genetic), TRIM67 (Affinity Capture-MS), USP27X (Affinity Capture-MS)

Disease & clinical

Genetic variants

Variant evidence for AMDHD2: 120 ClinVar records (6 pathogenic / likely pathogenic). Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	4
Uncertain significance	102
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (6)

Showing all 6 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
4073638	NM_001694.4(ATP6V0C):c.146C>T (p.Pro49Leu)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
3233449	NM_001694.4(ATP6V0C):c.283G>A (p.Ala95Thr)	Likely pathogenic	criteria provided, single submitter	1
59427	GRCh38/hg38 16p13.3(chr16:2494804-3246579)x1	Pathogenic	criteria provided, single submitter	1
3243524	NC_000016.9:g.(?2550259)(3154076_?)del	Pathogenic	criteria provided, single submitter	1
2685540	GRCh37/hg19 16p13.3(chr16:2480793-2590012)x1	Likely pathogenic	criteria provided, single submitter	1
152712	GRCh38/hg38 16p13.3(chr16:2406643-2782411)x1	Likely pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore AMDHD2’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 29 predictions of 804):

Position(s)	Effect	Δscore	Sites
16:2520530	donor_gain	1.0000
16:2520542–2520543	donor_loss	1.0000	5
16:2521124–2521125	donor_loss	1.0000	5
16:2527771–2527772	acceptor_loss	1.0000	3
16:2528229	acceptor_gain	1.0000
16:2528450	acceptor_loss	1.0000
16:2528451	acceptor_gain	1.0000
16:2528560–2528561	donor_loss	1.0000	5
16:2528648	acceptor_gain	1.0000
16:2520982–2520983	acceptor_loss	0.9900	6

AlphaMissense

938 missense substitutions predicted likely pathogenic (of 2,627 scored), across 254 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M237	9	0.856	0.976
D294	8	0.989	0.998
H211	8	0.986	0.995
H232	8	0.983	0.995
D269	8	0.964	0.987
H141	8	0.956	0.994
H272	8	0.950	0.987
H155	8	0.949	0.994
F234	8	0.928	0.994
D381	8	0.927	0.969
D79	8	0.924	0.965
D69	8	0.919	0.981
F80	8	0.897	0.984
H242	8	0.888	0.977
F240	8	0.877	0.970
H241	8	0.753	0.868
E143	7	0.984	0.996
F146	7	0.958	0.991
N73	7	0.951	0.991
N235	7	0.932	0.992

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Disease associations

OMIM: gene MIM:620864 | disease phenotypes: MIM:308350, MIM:616044, MIM:620465

GenCC curated gene-disease

Mondo (4): childhood-onset epilepsy syndrome (MONDO:0020072), developmental and epileptic encephalopathy, 1 (MONDO:0010632), autosomal dominant nonsyndromic hearing loss 65 (MONDO:0014470), epilepsy, early-onset, 3, with or without developmental delay (MONDO:0958196)

Orphanet (2): Childhood-onset epilepsy syndrome (Orphanet:98259), Rare autosomal dominant non-syndromic sensorineural deafness type DFNA (Orphanet:90635)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3217376 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

ChEMBL bioactivities

1 potent at pChembl≥5 of 1 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.47	Ki	34	nM	CHEMBL3219353

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, decreases expression	3
sodium arsenite	increases expression	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, affects expression	2
Ozone	affects cotreatment, increases oxidation, increases abundance, affects expression	2
Valproic Acid	increases expression, increases methylation	2
aristolochic acid I	decreases expression	1
bisphenol F	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
beta-lapachone	decreases expression, increases expression	1
butyraldehyde	increases expression	1
benzo(e)pyrene	decreases methylation	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
azoxystrobin	decreases expression	1
CGP 52608	affects binding, increases reaction	1
deguelin	decreases expression	1
pyrimidifen	decreases expression	1
bisphenol B	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pyrachlostrobin	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
bisphenol S	decreases methylation	1
jinfukang	affects cotreatment, increases expression	1
picoxystrobin	decreases expression	1
bisphenol AF	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Arsenic	affects methylation	1
Benzene	increases expression	1
Benzo(a)pyrene	increases methylation	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3223708	Binding	Inhibition of NagA (unknown origin)	The use of phosphate bioisosteres in medicinal chemistry and chemical biology — *Medchemcomm*

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for AMDHD2 across ~30M SureChEMBL compounds — explore on Sugi Predict.