HGH1

Summary

HGH1 (HGH1 cochaperone, HGNC:24161) is a protein-coding gene on chromosome 8q24.3, encoding Co-chaperone protein HGH1 homolog (Q9BTY7). Co-chaperone involved in the folding of nascent eukaryotic elongation factor eEF2, an essential component of the translation machinery.

At a glance

• Clinical variants (ClinVar): 9 total
• MANE Select transcript: NM_016458

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24161
Approved symbol	HGH1
Name	HGH1 cochaperone
Location	8q24.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ40907, LOC51236, Brp16
Ensembl gene	ENSG00000235173
Ensembl biotype	protein_coding
OMIM	620684
Entrez	51236

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 3 retained_intron, 2 protein_coding, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000347708, ENST00000525101, ENST00000530074, ENST00000530409, ENST00000533266, ENST00000534255, ENST00000628266

RefSeq mRNA: 1 — MANE Select: NM_016458 NM_016458

CCDS: CCDS6417

Canonical transcript exons

ENST00000347708 — 6 exons

Exon	Start	End
ENSE00001754243	144137774	144138428
ENSE00002167726	144139388	144140851
ENSE00003476080	144139009	144139100
ENSE00003514650	144138507	144138607
ENSE00003552730	144139189	144139311
ENSE00003618457	144138715	144138813

Expression profiles

Bgee: expression breadth ubiquitous, 253 present calls, max score 92.48.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.7450 / max 125.0914, expressed in 1777 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
205391	15.7450	1777

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
diaphragm	UBERON:0001103	92.48	gold quality
type B pancreatic cell	CL:0000169	89.60	gold quality
ileal mucosa	UBERON:0000331	89.50	gold quality
olfactory bulb	UBERON:0002264	89.28	gold quality
mucosa of transverse colon	UBERON:0004991	89.00	gold quality
apex of heart	UBERON:0002098	88.74	gold quality
hair follicle	UBERON:0002073	88.23	gold quality
pancreatic ductal cell	CL:0002079	88.22	silver quality
tibialis anterior	UBERON:0001385	88.11	gold quality
right adrenal gland	UBERON:0001233	87.79	gold quality
right adrenal gland cortex	UBERON:0035827	87.68	gold quality
right lobe of liver	UBERON:0001114	87.63	gold quality
granulocyte	CL:0000094	87.52	gold quality
right lobe of thyroid gland	UBERON:0001119	87.13	gold quality
left adrenal gland	UBERON:0001234	86.89	gold quality
left adrenal gland cortex	UBERON:0035825	86.74	gold quality
stromal cell of endometrium	CL:0002255	86.43	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.15	gold quality
adrenal cortex	UBERON:0001235	86.08	gold quality
hindlimb stylopod muscle	UBERON:0004252	86.07	gold quality
gastrocnemius	UBERON:0001388	85.66	gold quality
lower esophagus mucosa	UBERON:0035834	85.47	gold quality
adrenal gland	UBERON:0002369	85.03	gold quality
muscle of leg	UBERON:0001383	84.99	gold quality
left testis	UBERON:0004533	84.99	gold quality
left lobe of thyroid gland	UBERON:0001120	84.90	gold quality
muscle organ	UBERON:0001630	84.41	gold quality
right testis	UBERON:0004534	84.40	gold quality
metanephros cortex	UBERON:0010533	84.06	gold quality
quadriceps femoris	UBERON:0001377	84.01	silver quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.62

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

49 targeting HGH1, 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-4283	100.00	66.42	2097
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-7150	99.62	66.80	1322
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-4316	99.37	65.75	1360
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-4254	99.11	65.15	1315
HSA-MIR-485-5P	99.10	64.78	1889
HSA-MIR-6884-5P	99.10	64.50	1987
HSA-MIR-4434	99.10	67.01	1984
HSA-MIR-5703	99.10	67.09	2053
HSA-MIR-4270	99.02	66.26	1987

Literature-anchored findings (GeneRIF, showing 1)

• NSUN2/YBX1 promotes the progression of breast cancer by enhancing HGH1 mRNA stability through m[5]C methylation. (PMID:38844963)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	hgh1	ENSDARG00000101259
mus_musculus	Hgh1	ENSMUSG00000022554
rattus_norvegicus	Hgh1	ENSRNOG00000029238
drosophila_melanogaster	CG6073	FBGN0039417
caenorhabditis_elegans		WBGENE00021900

Protein

Protein identifiers

Co-chaperone protein HGH1 homolog — Q9BTY7 (reviewed: Q9BTY7)

All UniProt accessions (2): Q9BTY7, E9PIX0

UniProt curated annotations — full annotation on UniProt →

Function. Co-chaperone involved in the folding of nascent eukaryotic elongation factor eEF2, an essential component of the translation machinery. Recognizes a non-native conformation in the central domain of eEF2 and recruits the chaperonin-containing T-complex (TRiC) to the C-terminal region of the nascent polypeptide, preventing unproductive interactions and promoting efficient folding of the N-terminal GTPase domain. May also assist in eEF2 maturation by recruiting the molecular chaperone Hsp90.

Subunit / interactions. Forms a ternary complex wiht eEF2 and the chaperonin-containing T-complex (TRiC); mediates the interaction of eEF2 with TRiC. Interacts with CNS1; both could collaborate to recruit the CCT/TRiC and the Hsp90 chaperone systems for eEF2 folding.

Subcellular location. Cytoplasm.

Similarity. Belongs to the HGH1 family.

RefSeq proteins (1): NP_057542* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007205	Protein_HGH1_N	Domain
IPR007206	Protein_HGH1_C	Domain
IPR011989	ARM-like	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR039717	Hgh1	Family

Pfam: PF04063, PF04064

UniProt features (7 total): modified residue 4, initiator methionine 1, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BTY7-F1	91.47	0.81

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 (4): 2, 17, 214, 388

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 71 (showing top): MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, ACEVEDO_LIVER_CANCER_UP, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_UP, DURCHDEWALD_SKIN_CARCINOGENESIS_UP, LAIHO_COLORECTAL_CANCER_SERRATED_DN, NIKOLSKY_BREAST_CANCER_8Q23_Q24_AMPLICON, BAKKER_FOXO3_TARGETS_DN, FEVR_CTNNB1_TARGETS_DN, WAKABAYASHI_ADIPOGENESIS_PPARG_RXRA_BOUND_36HR, WAKABAYASHI_ADIPOGENESIS_PPARG_RXRA_BOUND_8D, SHEDDEN_LUNG_CANCER_GOOD_SURVIVAL_A12, chr8q24, ODONNELL_METASTASIS_UP, RPS14_DN.V1_DN, STK33_DN

GO Biological Process (0):

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

41 interactions, top by confidence:

A	B	Type	Score
TTC4	HGH1	psi-mi:“MI:0915”(physical association)	0.770
TTC4	EDRF1	psi-mi:“MI:0914”(association)	0.730
VAPB	FAM83G	psi-mi:“MI:0914”(association)	0.730
NTF3	BDNF	psi-mi:“MI:0914”(association)	0.590
ORF	EIF3D	psi-mi:“MI:0914”(association)	0.560
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
Cct4	ARHGAP32	psi-mi:“MI:0914”(association)	0.350
Cct2	OSBPL9	psi-mi:“MI:0914”(association)	0.350
Cct7	DTL	psi-mi:“MI:0914”(association)	0.350
Cct4		psi-mi:“MI:0914”(association)	0.350
Cct3	PFDN1	psi-mi:“MI:0914”(association)	0.350
Cct8	DTL	psi-mi:“MI:0914”(association)	0.350
	TBC1D1	psi-mi:“MI:0914”(association)	0.350
IMMP1L	EIF1AY	psi-mi:“MI:0914”(association)	0.350
IMMP2L	ANKHD1-EIF4EBP3	psi-mi:“MI:0914”(association)	0.350
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
ATG16L1		psi-mi:“MI:0914”(association)	0.350
KLHL14	ARHGAP32	psi-mi:“MI:0914”(association)	0.350
CAPN10	AHCYL1	psi-mi:“MI:0914”(association)	0.350
VWA2	RECQL4	psi-mi:“MI:0914”(association)	0.350
ELP4	HSPA8	psi-mi:“MI:0914”(association)	0.350
AFG2B	MMP24OS	psi-mi:“MI:0914”(association)	0.350
CIAO2A	MAP2K7	psi-mi:“MI:0914”(association)	0.350
CIB2	RIPK2	psi-mi:“MI:0914”(association)	0.350
EFNB2	TCAF2	psi-mi:“MI:0914”(association)	0.350
ELSPBP1	ADAM10	psi-mi:“MI:0914”(association)	0.350
ERF	DVL2	psi-mi:“MI:0914”(association)	0.350
HPN	DDX39A	psi-mi:“MI:0914”(association)	0.350

BioGRID (56): HGH1 (Affinity Capture-MS), HGH1 (Affinity Capture-MS), HGH1 (Affinity Capture-MS), HGH1 (Affinity Capture-MS), HGH1 (Affinity Capture-MS), HGH1 (Affinity Capture-MS), HGH1 (Affinity Capture-MS), HGH1 (Affinity Capture-MS), HGH1 (Affinity Capture-MS), HGH1 (Proximity Label-MS), HGH1 (Affinity Capture-MS), HGH1 (Affinity Capture-MS), TMEM256 (Two-hybrid), TRIT1 (Two-hybrid), APOM (Two-hybrid)

ESM2 similar proteins: A1A4L8, A1A4Q9, A1L134, A2BDX3, A5YM72, A6H707, B0BLZ5, B0JZP3, G3MZR2, O43292, O60831, O89109, P70295, Q11130, Q2TBP5, Q2V8X7, Q32NY4, Q3UPE3, Q4R4E4, Q4R4I9, Q5XIE1, Q5ZIW1, Q66HR0, Q6IQX7, Q6NRK8, Q6P2H8, Q7L1V2, Q80ZW2, Q86VU5, Q8IZ52, Q8N3Y3, Q8NE01, Q8NF37, Q8NI29, Q8TAC2, Q8TCD5, Q8TD43, Q8WUY1, Q92839, Q96DE0

Diamond homologs: P48362, Q10498, Q6DGR4, Q8C3I8, Q9BTY7, Q9VBG6, Q297A7, Q66KK3, Q6AY79, Q3KQ45, Q76NW7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

784 predictions. Top by Δscore:

Variant	Effect	Δscore
8:144138814:G:GG	donor_gain	1.0000
8:144139179:A:AG	acceptor_gain	1.0000
8:144139187:AGCT:A	acceptor_gain	1.0000
8:144139188:GCTG:G	acceptor_gain	1.0000
8:144139308:CCAG:C	donor_loss	1.0000
8:144139310:AG:A	donor_loss	1.0000
8:144139311:GG:G	donor_loss	1.0000
8:144139312:G:A	donor_loss	1.0000
8:144139313:T:A	donor_loss	1.0000
8:144139384:GCA:G	acceptor_loss	1.0000
8:144139384:GCAG:G	acceptor_loss	1.0000
8:144139385:CAGGT:C	acceptor_loss	1.0000
8:144139386:A:T	acceptor_loss	1.0000
8:144139387:G:A	acceptor_loss	1.0000
8:144138425:ACAG:A	donor_loss	0.9900
8:144138425:ACAGG:A	donor_loss	0.9900
8:144138426:CAG:C	donor_loss	0.9900
8:144138427:AGG:A	donor_loss	0.9900
8:144138427:AGGT:A	donor_loss	0.9900
8:144138428:GGTGA:G	donor_loss	0.9900
8:144138429:G:GA	donor_loss	0.9900
8:144138429:GTGAA:G	donor_loss	0.9900
8:144138430:T:A	donor_loss	0.9900
8:144138697:A:AG	acceptor_gain	0.9900
8:144138698:C:G	acceptor_gain	0.9900
8:144138703:A:AG	acceptor_gain	0.9900
8:144138704:C:G	acceptor_gain	0.9900
8:144138714:GGAC:G	acceptor_gain	0.9900
8:144138801:G:GT	donor_gain	0.9900
8:144138809:GCAAC:G	donor_gain	0.9900

AlphaMissense

2459 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:144138229:A:C	S132R	0.989
8:144138231:T:A	S132R	0.989
8:144138231:T:G	S132R	0.989
8:144138385:A:C	S184R	0.989
8:144138387:C:A	S184R	0.989
8:144138387:C:G	S184R	0.989
8:144138591:T:A	N226K	0.979
8:144138591:T:G	N226K	0.979
8:144138595:T:C	C228R	0.978
8:144139211:G:C	R303P	0.978
8:144138597:C:G	C228W	0.976
8:144138730:T:C	L237S	0.976
8:144139256:T:C	L318P	0.974
8:144138592:T:C	C227R	0.970
8:144138587:G:C	R225P	0.969
8:144139071:C:A	R286S	0.969
8:144139072:G:C	R286P	0.969
8:144139089:G:C	A292P	0.967
8:144138381:C:A	N182K	0.966
8:144138381:C:G	N182K	0.966
8:144139250:G:C	R316P	0.965
8:144138596:G:A	C228Y	0.964
8:144139392:T:A	L338H	0.964
8:144138581:C:A	T223K	0.963
8:144139392:T:C	L338P	0.963
8:144138775:T:C	L252S	0.958
8:144139012:T:C	L266P	0.958
8:144139304:T:C	L334P	0.957
8:144139195:G:C	A298P	0.956
8:144138766:T:C	L249P	0.954

dbSNP variants (sampled 300 via entrez): RS1000132029 (8:144140959 G>A), RS1000484401 (8:144141173 C>T), RS1001083812 (8:144140145 C>T), RS1001523380 (8:144136612 G>C), RS1001536813 (8:144139950 C>T), RS1001592113 (8:144136849 G>A), RS1003192165 (8:144137810 C>A,G,T), RS1003262916 (8:144138385 A>G), RS1003979146 (8:144140676 A>C), RS1004315119 (8:144140545 C>A,T), RS1004870623 (8:144139378 C>T), RS1004942662 (8:144139638 C>T), RS1006037884 (8:144136522 C>T), RS1006095026 (8:144136322 T>C), RS1006756351 (8:144139051 G>A)

Disease associations

OMIM: gene MIM:620684 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	3
FR900359	increases phosphorylation	1
bisphenol F	affects cotreatment, increases expression	1
bisphenol A	increases expression	1
cobaltous chloride	decreases expression	1
ferrous chloride	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
ICG 001	increases expression	1
NSC 689534	affects binding, decreases expression	1
MT19c compound	decreases expression	1
Temozolomide	increases expression	1
Cadmium	increases expression	1
Copper	affects binding, decreases expression	1
Dexamethasone	increases expression, affects cotreatment	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Indomethacin	increases expression, affects cotreatment	1
Ivermectin	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Silicon Dioxide	increases expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	decreases expression	1
Valproic Acid	increases methylation	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Palmitic Acid	decreases expression	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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