HIGD1C

Summary

HIGD1C (HIG1 hypoxia inducible domain family member 1C, HGNC:28044) is a protein-coding gene on chromosome 12q13.12, encoding HIG1 domain family member 1C (A8MV81).

Predicted to be involved in mitochondrial respirasome assembly. Predicted to act upstream of or within response to hypoxia. Predicted to be located in mitochondrial membrane. Predicted to be active in mitochondrion.

Source: NCBI Gene 613227 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 13 total
• MANE Select transcript: NM_001109619

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28044
Approved symbol	HIGD1C
Name	HIG1 hypoxia inducible domain family member 1C
Location	12q13.12
Locus type	gene with protein product
Status	Approved
Aliases	Gm921
Ensembl gene	ENSG00000214511
Ensembl biotype	protein_coding
OMIM	620803
Entrez	613227

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000398455, ENST00000695930, ENST00000695931

RefSeq mRNA: 1 — MANE Select: NM_001109619 NM_001109619

CCDS: CCDS44882

Canonical transcript exons

ENST00000695931 — 5 exons

Exon	Start	End
ENSE00001533227	50960968	50961102
ENSE00003965511	50970442	50970607
ENSE00003965512	50952544	50952715
ENSE00003965514	50953991	50954092
ENSE00003965516	50953205	50953259

Expression profiles

Bgee: expression breadth ubiquitous, 121 present calls, max score 91.96.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.96	gold quality
corpus callosum	UBERON:0002336	65.81	gold quality
fundus of stomach	UBERON:0001160	58.71	gold quality
granulocyte	CL:0000094	58.35	gold quality
ectocervix	UBERON:0012249	56.16	gold quality
descending thoracic aorta	UBERON:0002345	56.05	gold quality
left uterine tube	UBERON:0001303	52.83	gold quality
fallopian tube	UBERON:0003889	52.56	gold quality
omental fat pad	UBERON:0010414	51.90	gold quality
body of uterus	UBERON:0009853	51.70	gold quality
adipose tissue	UBERON:0001013	51.28	gold quality
monocyte	CL:0000576	51.26	gold quality
cerebellar hemisphere	UBERON:0002245	51.03	gold quality
subcutaneous adipose tissue	UBERON:0002190	51.01	gold quality
left ovary	UBERON:0002119	50.93	gold quality
left lobe of thyroid gland	UBERON:0001120	50.92	gold quality
tibial nerve	UBERON:0001323	50.92	gold quality
left coronary artery	UBERON:0001626	50.90	gold quality
right hemisphere of cerebellum	UBERON:0014890	50.89	gold quality
cerebellar cortex	UBERON:0002129	50.63	gold quality
leukocyte	CL:0000738	50.45	gold quality
cerebellum	UBERON:0002037	50.37	gold quality
thyroid gland	UBERON:0002046	50.36	gold quality
mucosa of transverse colon	UBERON:0004991	50.34	gold quality
uterine cervix	UBERON:0000002	49.97	gold quality
right lung	UBERON:0002167	49.87	gold quality
endometrium	UBERON:0001295	49.60	gold quality
calcaneal tendon	UBERON:0003701	49.38	gold quality
right lobe of liver	UBERON:0001114	49.19	gold quality
left testis	UBERON:0004533	48.74	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.11

Regulation

Is transcription factor: no

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	higd1a	ENSDARG00000022303
mus_musculus	Higd1c	ENSMUSG00000093550
rattus_norvegicus	Higd1c	ENSRNOG00000046069
drosophila_melanogaster	CG9921	FBGN0030743
drosophila_melanogaster	CG11825	FBGN0033519
caenorhabditis_elegans		WBGENE00011859

Paralogs (4): HIGD1B (ENSG00000131097), HIGD2A (ENSG00000146066), HIGD2B (ENSG00000175202), HIGD1A (ENSG00000181061)

Protein

Protein identifiers

HIG1 domain family member 1C — A8MV81 (reviewed: A8MV81)

All UniProt accessions (2): A0A8Q3SID1, A8MV81

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

RefSeq proteins (1): NP_001103089* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007667	Hypoxia_induced_domain	Domain
IPR050355	RCF1	Family

Pfam: PF04588

UniProt features (7 total): topological domain 3, transmembrane region 2, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A8MV81-F1	63.59	0.00

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-5628897	TP53 Regulates Metabolic Genes
R-HSA-611105	Respiratory electron transport
R-HSA-9707564	Cytoprotection by HMOX1

MSigDB gene sets: 49 (showing top): GOBP_MITOCHONDRIAL_RESPIRATORY_CHAIN_COMPLEX_ASSEMBLY, GOBP_RESPONSE_TO_OXYGEN_LEVELS, GOBP_RESPONSE_TO_ABIOTIC_STIMULUS, MTOR_UP.V1_DN, REACTOME_TRANSCRIPTIONAL_REGULATION_BY_TP53, REACTOME_TP53_REGULATES_METABOLIC_GENES, ESC_V6.5_UP_EARLY.V1_UP, REACTOME_CELLULAR_RESPONSES_TO_STIMULI, GOBP_MITOCHONDRION_ORGANIZATION, GSE13493_DP_VS_CD8POS_THYMOCYTE_UP, GOBP_MITOCHONDRIAL_RESPIRASOME_ASSEMBLY, SMN1_SMN2_TARGET_GENES, GSE17721_POLYIC_VS_PAM3CSK4_6H_BMDC_UP, GSE17721_LPS_VS_GARDIQUIMOD_24H_BMDC_UP, GSE17721_0.5H_VS_8H_PAM3CSK4_BMDC_UP

GO Biological Process (2): response to hypoxia (GO:0001666), mitochondrial respirasome assembly (GO:0097250)

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

GO Cellular Component (3): mitochondrion (GO:0005739), membrane (GO:0016020), mitochondrial membrane (GO:0031966)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Transcriptional Regulation by TP53	1
Aerobic respiration and respiratory electron transport	1
Cellular response to chemical stress	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
response to stress	1
response to decreased oxygen levels	1
mitochondrion organization	1
mitochondrial respiratory chain complex assembly	1
binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1
mitochondrion	1
mitochondrial envelope	1
organelle membrane	1

Protein interactions and networks

STRING

356 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HIGD1C	COQ5	Q5HYK3	785
HIGD1C	COQ3	Q9NZJ6	571
HIGD1C	C21orf140	B9A014	518
HIGD1C	CXorf66	Q5JRM2	480
HIGD1C	COQ8B	Q96D53	448
HIGD1C	COQ8A	Q8NI60	445
HIGD1C	COQ4	Q9Y3A0	440
HIGD1C	PDSS1	Q5T2R2	417
HIGD1C	TEX29	Q8N6K0	414
HIGD1C	RBX1	P62877	410
HIGD1C	COQ6	Q9Y2Z9	400
HIGD1C	C1orf53	Q5VUE5	400
HIGD1C	COQ7	Q99807	380
HIGD1C	METTL2B	Q6P1Q9	370
HIGD1C	HEMK1	Q9Y5R4	338

IntAct

46 interactions, top by confidence:

A	B	Type	Score
HIGD1C	TCEA2	psi-mi:“MI:0915”(physical association)	0.560
HIGD1C	CYB5R1	psi-mi:“MI:0915”(physical association)	0.560
	HIGD1C	psi-mi:“MI:0915”(physical association)	0.560
HIGD1C	GAD2	psi-mi:“MI:0915”(physical association)	0.560
HIGD1C	SYT16	psi-mi:“MI:0915”(physical association)	0.560
HIGD1C	PBX3	psi-mi:“MI:0915”(physical association)	0.560
HIGD1C	FARS2	psi-mi:“MI:0915”(physical association)	0.560
HIGD1C	RBFA	psi-mi:“MI:0915”(physical association)	0.560
HIGD1C	MTERF3	psi-mi:“MI:0915”(physical association)	0.560
HIGD1C	NTAQ1	psi-mi:“MI:0915”(physical association)	0.560
HIGD1C	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
HIGD1C	CIDEB	psi-mi:“MI:0915”(physical association)	0.560
HIGD1C	APOC1	psi-mi:“MI:0915”(physical association)	0.560
PRKAR1A	RBFOX3	psi-mi:“MI:0914”(association)	0.350
PAK1		psi-mi:“MI:0914”(association)	0.350
HDAC1	HIGD1C	psi-mi:“MI:0914”(association)	0.350
EDEM2	HIGD1C	psi-mi:“MI:0914”(association)	0.350
LCN6	HIGD1C	psi-mi:“MI:0914”(association)	0.350
TCEA2	HIGD1C	psi-mi:“MI:0915”(physical association)	0.000
CYB5R1	HIGD1C	psi-mi:“MI:0915”(physical association)	0.000
HIGD1C		psi-mi:“MI:0915”(physical association)	0.000
NTAQ1	HIGD1C	psi-mi:“MI:0915”(physical association)	0.000
GAD2	HIGD1C	psi-mi:“MI:0915”(physical association)	0.000
SYT16	HIGD1C	psi-mi:“MI:0915”(physical association)	0.000
PBX3	HIGD1C	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (17): HIGD1C (Two-hybrid), HIGD1C (Two-hybrid), HIGD1C (Two-hybrid), HIGD1C (Two-hybrid), HIGD1C (Two-hybrid), HIGD1C (Two-hybrid), HIGD1C (Two-hybrid), HIGD1C (Two-hybrid), HIGD1C (Two-hybrid), HIGD1C (Two-hybrid), HIGD1C (Two-hybrid), HIGD1C (Two-hybrid), HIGD1C (Two-hybrid), HIGD1C (Affinity Capture-MS), HIGD1C (Affinity Capture-MS)

ESM2 similar proteins: A1CHC5, A3LVL1, A5E2M7, A6RBB3, A6ZM32, A7TFU8, A8MV81, B3LLM2, B6K2Z6, B9WHT6, C0NUL6, C0RYW2, C1G794, C4QV79, C4Y631, C4YRP9, C5DE77, C5DLZ7, C5DWC4, C5FSQ7, C5GDJ2, C5JIT3, C5MAV2, C6H220, C7GT60, C8ZEH4, D4DDK2, P53721, P63031, P79082, P81928, Q03713, Q21828, Q3ZCG2, Q59N74, Q5NVQ1, Q6CBQ8, Q6CWT4, Q6FSW5, Q756G1

Diamond homologs: A8MV81, C7YJ02, C9SF29, Q4VC39, Q5NVQ1, Q76I25, Q8VH49, Q99JY6, Q9BW72, Q9CQJ1, Q9JLR9, Q9P298, Q9Y241, A1CHC5, A1CXG2, A2QI79, A3LVL1, A4RI25, A5DHC2, A5E2M7, A6RBB3, A6SSX6, A6ZM32, A7F679, A7TFU8, A8P006, B0D4J7, B0Y606, B2WBP3, B3LLM2, B6H465, B6K2Z6, B6QHL8, B6QHL9, B8MJJ2, B8N9M0, B9WHT6, C0NUL6, C0RYW2, C1G794

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	9
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

437 predictions. Top by Δscore:

Variant	Effect	Δscore
12:50954089:ATAGG:A	donor_loss	0.9900
12:50954090:TAGGT:T	donor_loss	0.9900
12:50954091:AGGT:A	donor_loss	0.9900
12:50954093:GTAA:G	donor_loss	0.9900
12:50954094:T:A	donor_loss	0.9900
12:50954061:G:GT	donor_gain	0.9800
12:50954093:G:GG	donor_gain	0.9800
12:50954088:TATAG:T	donor_gain	0.9600
12:50954089:ATAG:A	donor_gain	0.9600
12:50954090:TAG:T	donor_gain	0.9600
12:50954091:AG:A	donor_gain	0.9400
12:50954092:GG:G	donor_gain	0.9400
12:50954062:A:T	donor_gain	0.9300
12:50962025:A:T	acceptor_gain	0.8700
12:50957338:G:GG	donor_gain	0.8300
12:50961098:TCTAG:T	donor_loss	0.7900
12:50961099:CTAG:C	donor_loss	0.7900
12:50961100:TAG:T	donor_loss	0.7900
12:50961101:AG:A	donor_loss	0.7900
12:50961102:GGTA:G	donor_loss	0.7900
12:50961103:GT:G	donor_loss	0.7900
12:50961104:TAA:T	donor_loss	0.7900
12:50961105:A:T	donor_loss	0.7900
12:50954095:AA:A	donor_loss	0.7700
12:50960958:A:G	acceptor_loss	0.7400
12:50960962:TCACA:T	acceptor_loss	0.7400
12:50960963:CACA:C	acceptor_loss	0.7400
12:50960964:ACAGG:A	acceptor_loss	0.7400
12:50960965:CA:C	acceptor_loss	0.7400
12:50960966:A:C	acceptor_loss	0.7400

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000025217 (12:50938474 G>A), RS1000188243 (12:50955485 G>A), RS1000202302 (12:50948265 T>C), RS1000302643 (12:50955054 G>A,C), RS1000389699 (12:50962487 G>A,T), RS1000398972 (12:50961456 G>A), RS1000499560 (12:50956937 G>A), RS1000665286 (12:50942172 G>A,T), RS1000826303 (12:50948628 G>C), RS1000864742 (12:50942487 A>G), RS1000896359 (12:50935979 G>C), RS1000941471 (12:50950125 A>G), RS1001051993 (12:50951637 G>A), RS1001059608 (12:50958318 G>A), RS1001082874 (12:50951876 T>C,G)

Disease associations

OMIM: gene MIM:620803 | 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

2 total (human), top 2 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases methylation	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

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