GHDC

Summary

GHDC (GH3 domain containing, HGNC:24438) is a protein-coding gene on chromosome 17q21.2, encoding GH3 domain-containing protein (Q8N2G8).

Predicted to enable acid-amino acid ligase activity. Located in membrane.

Source: NCBI Gene 84514 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 101 total
• Druggable target: yes
• MANE Select transcript: NM_032484

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24438
Approved symbol	GHDC
Name	GH3 domain containing
Location	17q21.2
Locus type	gene with protein product
Status	Approved
Aliases	LGP1
Ensembl gene	ENSG00000167925
Ensembl biotype	protein_coding
OMIM	608587
Entrez	84514

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 10 protein_coding, 2 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000301671, ENST00000414034, ENST00000585375, ENST00000585735, ENST00000586692, ENST00000587427, ENST00000588352, ENST00000588762, ENST00000590249, ENST00000590520, ENST00000593209, ENST00000853516, ENST00000853517, ENST00000965653, ENST00000965654

RefSeq mRNA: 2 — MANE Select: NM_032484 NM_001142623, NM_032484

CCDS: CCDS11422, CCDS45682

Canonical transcript exons

ENST00000587427 — 10 exons

Exon	Start	End
ENSE00001118423	42192906	42193027
ENSE00001670960	42191018	42191210
ENSE00001689763	42190624	42190757
ENSE00001711048	42190185	42190270
ENSE00002256945	42192241	42192742
ENSE00002289994	42193767	42193850
ENSE00002790894	42189087	42189921
ENSE00002884002	42194393	42194494
ENSE00003481186	42190832	42190903
ENSE00003499549	42193317	42193594

Expression profiles

Bgee: expression breadth ubiquitous, 211 present calls, max score 92.60.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.9423 / max 162.4997, expressed in 1712 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
166113	6.1647	1688
166112	0.7776	446

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right adrenal gland cortex	UBERON:0035827	92.60	gold quality
right adrenal gland	UBERON:0001233	92.10	gold quality
left adrenal gland cortex	UBERON:0035825	91.85	gold quality
left adrenal gland	UBERON:0001234	91.63	gold quality
granulocyte	CL:0000094	91.59	gold quality
adrenal cortex	UBERON:0001235	90.86	gold quality
right lobe of thyroid gland	UBERON:0001119	90.73	gold quality
spleen	UBERON:0002106	90.65	gold quality
kidney epithelium	UBERON:0004819	90.34	gold quality
adrenal gland	UBERON:0002369	90.15	gold quality
parotid gland	UBERON:0001831	89.95	gold quality
left lobe of thyroid gland	UBERON:0001120	89.77	gold quality
right ovary	UBERON:0002118	89.11	gold quality
left ovary	UBERON:0002119	89.11	gold quality
ileal mucosa	UBERON:0000331	89.04	gold quality
metanephros cortex	UBERON:0010533	88.78	gold quality
thyroid gland	UBERON:0002046	88.74	gold quality
body of pancreas	UBERON:0001150	88.46	gold quality
right hemisphere of cerebellum	UBERON:0014890	88.45	gold quality
stromal cell of endometrium	CL:0002255	88.36	gold quality
cerebellar hemisphere	UBERON:0002245	87.93	gold quality
body of stomach	UBERON:0001161	87.91	gold quality
right uterine tube	UBERON:0001302	87.90	gold quality
cerebellar cortex	UBERON:0002129	87.80	gold quality
endocervix	UBERON:0000458	87.78	gold quality
apex of heart	UBERON:0002098	87.75	gold quality
cortex of kidney	UBERON:0001225	87.67	gold quality
right coronary artery	UBERON:0001625	87.43	gold quality
small intestine Peyer’s patch	UBERON:0003454	87.30	gold quality
ascending aorta	UBERON:0001496	87.15	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.99

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

18 targeting GHDC, 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-4481	100.00	66.42	1669
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-4679	99.76	69.19	1229
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-6761-5P	98.71	68.03	1504
HSA-MIR-3668	98.52	68.76	951
HSA-MIR-6827-5P	98.46	64.88	1256
HSA-MIR-6780A-3P	98.42	67.49	1518
HSA-MIR-5585-5P	97.95	68.80	1024
HSA-MIR-6893-3P	97.79	64.91	1238
HSA-MIR-3620-5P	97.42	63.95	792
HSA-MIR-370-3P	97.09	64.92	1221
HSA-MIR-4448	97.04	66.22	752
HSA-MIR-1587	96.95	64.03	932
HSA-MIR-1251-5P	95.78	64.10	374

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ghdc	ENSDARG00000055569
mus_musculus	Ghdc	ENSMUSG00000017747
rattus_norvegicus	Ghdc	ENSRNOG00000018906

Protein

Protein identifiers

GH3 domain-containing protein — Q8N2G8 (reviewed: Q8N2G8)

All UniProt accessions (5): Q8N2G8, K7EJT7, K7EL54, K7EQ41, K7ESN3

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Endoplasmic reticulum. Nucleus envelope.

Post-translational modifications. Methylated at Gln-489 by N6AMT1.

Similarity. Belongs to the GH3 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8N2G8-1	1	yes
Q8N2G8-2	2
Q8N2G8-3	3

RefSeq proteins (2): NP_001136095, NP_115873* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004993	GH3	Family
IPR055377	GH3_M	Domain
IPR055378	GH3_C	Domain
IPR056985	GH3_N	Domain

Pfam: PF23571, PF23572, PF25146

UniProt features (10 total): splice variant 3, signal peptide 1, chain 1, region of interest 1, modified residue 1, glycosylation site 1, mutagenesis site 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N2G8-F1	82.77	0.55

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 (1): 489

Glycosylation sites (1): 450

Mutagenesis-validated functional residues (1):

Position	Phenotype
489	abolishes methylation by n6amt1.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation

MSigDB gene sets: 84 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, GOCC_SECRETORY_GRANULE, SP3_Q3, AREB6_03, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, CHANDRAN_METASTASIS_DN, TGIF_01, MYOD_Q6, GOMF_LIGASE_ACTIVITY_FORMING_CARBON_NITROGEN_BONDS, GOMF_ACID_AMINO_ACID_LIGASE_ACTIVITY, GOCC_NUCLEAR_ENVELOPE, GOCC_SECRETORY_VESICLE, GOCC_VESICLE_LUMEN, GOCC_SPECIFIC_GRANULE

GO Biological Process (0):

GO Molecular Function (1): acid-amino acid ligase activity (GO:0016881)

GO Cellular Component (8): extracellular region (GO:0005576), nuclear envelope (GO:0005635), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), membrane (GO:0016020), secretory granule lumen (GO:0034774), specific granule lumen (GO:0035580), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Innate Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
endomembrane system	2
intracellular membrane-bounded organelle	2
ligase activity, forming carbon-nitrogen bonds	1
nucleus	1
organelle envelope	1
intracellular anatomical structure	1
cytoplasm	1
secretory granule	1
cytoplasmic vesicle lumen	1
secretory granule lumen	1
specific granule	1

Protein interactions and networks

STRING

282 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GHDC	CAVIN1	Q6NZI2	818
GHDC	HCRT	O43612	762
GHDC	STAT5B	P51692	693
GHDC	DHX58	Q96C10	690
GHDC	STAT5A	P42229	668
GHDC	STAT3	P40763	576
GHDC	KCNH4	Q9UQ05	549
GHDC	SEC23IP	Q9Y6Y8	320
GHDC	OSM	P13725	318
GHDC	KAT2A	Q92830	317
GHDC	PPP1R12A	O14974	232
GHDC	LDHD	Q86WU2	204
GHDC	GUK1	Q16774	204
GHDC	AZI2	Q9H6S1	204
GHDC	NUP85	Q9BW27	203

IntAct

80 interactions, top by confidence:

A	B	Type	Score
ENTREP1	WWP2	psi-mi:“MI:0914”(association)	0.850
NIPAL1	ESYT2	psi-mi:“MI:0914”(association)	0.640
TRDN	TMEM223	psi-mi:“MI:0914”(association)	0.640
KCNA5	TMEM223	psi-mi:“MI:0914”(association)	0.530
TSPAN17	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
CHRNA9	CHEK1	psi-mi:“MI:0914”(association)	0.530
SLC22A15	ZFPL1	psi-mi:“MI:0914”(association)	0.530
SEC11C	APOM	psi-mi:“MI:0914”(association)	0.530
ATP5MC3	ATP5F1B	psi-mi:“MI:0914”(association)	0.530
SIDT2	AP3D1	psi-mi:“MI:0914”(association)	0.530
AAR2	SNRNP200	psi-mi:“MI:0914”(association)	0.530
SLC30A2	ESYT2	psi-mi:“MI:0914”(association)	0.530
SLC6A8	ILVBL	psi-mi:“MI:0914”(association)	0.530
CXCR5	GHDC	psi-mi:“MI:0915”(physical association)	0.400
OR2A25	GHDC	psi-mi:“MI:0915”(physical association)	0.400
Timeless	TRAPPC13	psi-mi:“MI:0914”(association)	0.350
LRP8	TYK2	psi-mi:“MI:0914”(association)	0.350
CXCR3	GHDC	psi-mi:“MI:0914”(association)	0.350
	MYO9A	psi-mi:“MI:0914”(association)	0.350
ATG2A	ESYT2	psi-mi:“MI:0914”(association)	0.350
Npc1	ESYT2	psi-mi:“MI:0914”(association)	0.350
KCNA2	TMEM129	psi-mi:“MI:0914”(association)	0.350
ATP2B2	ESYT2	psi-mi:“MI:0914”(association)	0.350
IGHM	ESYT2	psi-mi:“MI:0914”(association)	0.350
TTMP	TMEM223	psi-mi:“MI:0914”(association)	0.350
TTYH1	TMEM223	psi-mi:“MI:0914”(association)	0.350
TSPAN15	TMEM223	psi-mi:“MI:0914”(association)	0.350
CHRNA3	TMEM223	psi-mi:“MI:0914”(association)	0.350
CHRNA4	TMEM223	psi-mi:“MI:0914”(association)	0.350

BioGRID (112): GHDC (Affinity Capture-MS), GHDC (Affinity Capture-MS), GHDC (Affinity Capture-MS), GHDC (Affinity Capture-MS), GHDC (Affinity Capture-MS), GHDC (Affinity Capture-MS), GHDC (Affinity Capture-MS), GHDC (Affinity Capture-MS), GHDC (Affinity Capture-MS), GHDC (Affinity Capture-MS), GHDC (Affinity Capture-MS), GHDC (Affinity Capture-MS), GHDC (Affinity Capture-MS), GHDC (Affinity Capture-MS), GHDC (Affinity Capture-MS)

ESM2 similar proteins: A4GXA9, A7E3N7, A8VU90, D3KCC4, D3ZZN9, G3V8H4, O08672, O95382, Q13608, Q13671, Q14296, Q17RN3, Q28616, Q3UR50, Q3UR97, Q3V3V9, Q4KM32, Q53GL7, Q56A04, Q58CQ5, Q58EX7, Q5BK61, Q5NVA9, Q62893, Q643R3, Q66H85, Q6F5E8, Q6NVH7, Q6ZW31, Q7T0L4, Q80UU1, Q80XL1, Q8BJW7, Q8BTN6, Q8CIE4, Q8CJ00, Q8K592, Q8N2G8, Q8NAG6, Q8VCI7

Diamond homologs: A0A1J6KGJ9, A0A314KSQ4, A3BLS0, O22190, O81829, O82243, O82333, P0C0M2, P0C0M3, Q0D4Z6, Q2R3B4, Q53P49, Q5NAZ7, Q60EJ6, Q60EY1, Q654M1, Q6I581, Q6ZLA3, Q6ZLA7, Q8GZ29, Q8LQM5, Q8N2G8, Q9FZ87, Q9LQ68, Q9LSQ4, Q9LYU4, Q9SKE2, Q9SZT9, Q9ZNS2, Q99J23

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 106 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
R-HSA-425366	6	17.0×	3e-04
SLC-mediated transmembrane transport	8	7.4×	1e-03
Neuronal System	8	5.5×	2e-03
Transport of small molecules	10	3.9×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
zinc ion transmembrane transport	5	38.2×	3e-05
membrane depolarization	5	27.8×	9e-05
regulation of membrane potential	9	22.6×	1e-07
amino acid transport	6	20.4×	7e-05
monoatomic ion transmembrane transport	6	13.6×	4e-04
sodium ion transmembrane transport	5	11.0×	4e-03
transport across blood-brain barrier	5	9.7×	6e-03
monoatomic ion transport	5	8.5×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	82
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1052 predictions. Top by Δscore:

Variant	Effect	Δscore
17:42190827:CCTA:C	donor_loss	1.0000
17:42190828:CTA:C	donor_loss	1.0000
17:42190829:TA:T	donor_loss	1.0000
17:42190830:A:T	donor_loss	1.0000
17:42190831:C:CA	donor_loss	1.0000
17:42190901:CACCT:C	acceptor_loss	1.0000
17:42190902:ACCTG:A	acceptor_loss	1.0000
17:42190903:CCTG:C	acceptor_loss	1.0000
17:42190905:T:G	acceptor_loss	1.0000
17:42191013:ATCAC:A	donor_loss	1.0000
17:42191014:TCACC:T	donor_loss	1.0000
17:42191015:CAC:C	donor_loss	1.0000
17:42191016:AC:A	donor_loss	1.0000
17:42191017:C:A	donor_loss	1.0000
17:42191206:CACCC:C	acceptor_gain	1.0000
17:42191208:CCC:C	acceptor_gain	1.0000
17:42191209:CC:C	acceptor_gain	1.0000
17:42191209:CCCTG:C	acceptor_gain	1.0000
17:42191210:CC:C	acceptor_gain	1.0000
17:42191210:CCTGT:C	acceptor_loss	1.0000
17:42191211:C:CC	acceptor_gain	1.0000
17:42190830:A:AC	donor_gain	0.9900
17:42190831:C:CC	donor_gain	0.9900
17:42190831:CCTG:C	donor_gain	0.9900
17:42190901:CAC:C	acceptor_gain	0.9900
17:42190904:C:CC	acceptor_gain	0.9900
17:42190907:A:AC	acceptor_gain	0.9900
17:42190907:A:C	acceptor_gain	0.9900
17:42190912:G:C	acceptor_gain	0.9900
17:42191012:GATCA:G	donor_loss	0.9900

AlphaMissense

3317 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:42190233:A:C	F442L	0.962
17:42190233:A:T	F442L	0.962
17:42190235:A:G	F442L	0.962
17:42192364:A:G	W256R	0.957
17:42192364:A:T	W256R	0.957
17:42191018:C:A	R361M	0.956
17:42192362:C:A	W256C	0.942
17:42192362:C:G	W256C	0.942
17:42192501:A:G	F210S	0.932
17:42190675:A:G	W413R	0.928
17:42190675:A:T	W413R	0.928
17:42189820:G:C	F492L	0.927
17:42189820:G:T	F492L	0.927
17:42189822:A:G	F492L	0.927
17:42190634:G:C	S426R	0.926
17:42190634:G:T	S426R	0.926
17:42190636:T:G	S426R	0.926
17:42190847:A:T	V380D	0.926
17:42189888:A:C	Y470D	0.921
17:42190234:A:G	F442S	0.913
17:42190673:C:A	W413C	0.912
17:42190673:C:G	W413C	0.912
17:42192375:G:T	A252D	0.912
17:42191018:C:G	R361T	0.911
17:42190903:C:A	R361S	0.910
17:42190903:C:G	R361S	0.910
17:42190840:G:C	F382L	0.908
17:42190840:G:T	F382L	0.908
17:42190842:A:G	F382L	0.908
17:42189887:T:G	Y470S	0.907

dbSNP variants (sampled 300 via entrez): RS1000486597 (17:42191176 G>A), RS1000988023 (17:42196173 C>T), RS1002323185 (17:42191844 T>C), RS1002437716 (17:42191548 C>A,T), RS1002996067 (17:42194735 C>G), RS1003108697 (17:42194414 T>C), RS1003328200 (17:42193249 C>G,T), RS1003514445 (17:42194450 T>G), RS1003823280 (17:42194283 C>A,G,T), RS1005550161 (17:42189447 A>C,G), RS1006331808 (17:42188978 C>T), RS1006361492 (17:42189200 C>T), RS1007356017 (17:42195612 C>T), RS1007832059 (17:42195986 G>A), RS1008910768 (17:42192445 G>C)

Disease associations

OMIM: gene MIM:608587 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST007995_3	Asthma (childhood onset)	5.000000e-09

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066372 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol S	affects cotreatment, increases expression, increases methylation	2
Rotenone	increases expression	2
GSK-J4	decreases expression	1
FR900359	increases phosphorylation	1
bisphenol F	affects cotreatment, increases expression	1
bisphenol A	increases expression, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
entinostat	increases expression	1
ICG 001	decreases expression	1
abrine	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Temozolomide	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Cisplatin	affects cotreatment, increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Ozone	affects expression, increases abundance	1
Quercetin	increases expression	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1
Tretinoin	increases expression	1
Valproic Acid	increases methylation	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Copper Sulfate	decreases expression	1
Acrylamide	decreases expression	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
CHEMBL5651471	Binding	Binding affinity to human GHDC incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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