HYCC2

Summary

HYCC2 (hyccin PI4KA lipid kinase complex subunit 2, HGNC:28593) is a protein-coding gene on chromosome 2q33.1, encoding Hyccin 2 (Q8IXS8). Component of a complex required to localize phosphatidylinositol 4-kinase (PI4K) to the plasma membrane.

Predicted to be involved in phosphatidylinositol phosphate biosynthetic process and protein localization to plasma membrane. Predicted to be located in cytosol and membrane. Predicted to be active in plasma membrane.

Source: NCBI Gene 285172 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 72 total
• MANE Select transcript: NM_001321623

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28593
Approved symbol	HYCC2
Name	hyccin PI4KA lipid kinase complex subunit 2
Location	2q33.1
Locus type	gene with protein product
Status	Approved
Aliases	MGC39518
Ensembl gene	ENSG00000155744
Ensembl biotype	protein_coding
Entrez	285172

Gene structure

Transcript identifiers

Ensembl transcripts: 42 — 35 protein_coding, 5 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000286181, ENST00000418596, ENST00000446678, ENST00000452799, ENST00000453765, ENST00000474118, ENST00000485144, ENST00000485636, ENST00000490725, ENST00000494881, ENST00000498780, ENST00000681958, ENST00000861781, ENST00000861782, ENST00000861783, ENST00000861784, ENST00000861785, ENST00000861786, ENST00000861787, ENST00000861788, ENST00000861789, ENST00000861790, ENST00000861791, ENST00000861792, ENST00000861793, ENST00000861794, ENST00000861795, ENST00000861796, ENST00000861797, ENST00000861798, ENST00000861799, ENST00000861800, ENST00000861801, ENST00000861802, ENST00000861803, ENST00000861804, ENST00000944413, ENST00000944414, ENST00000944415, ENST00000944416, ENST00000944417, ENST00000944418

RefSeq mRNA: 12 — MANE Select: NM_001321623 NM_001321618, NM_001321619, NM_001321621, NM_001321622, NM_001321623, NM_001321624, NM_001321625, NM_001321626, NM_001321627, NM_001321628, NM_001321629, NM_173822

CCDS: CCDS2335, CCDS92921

Canonical transcript exons

ENST00000681958 — 13 exons

Exon	Start	End
ENSE00001260703	201045496	201045593
ENSE00001660961	200973718	200981871
ENSE00001903223	201071610	201071671
ENSE00003473608	200988262	200988421
ENSE00003586221	201022831	201022932
ENSE00003588801	201023959	201024039
ENSE00003615910	201016991	201017170
ENSE00003627733	201008973	201009088
ENSE00003649532	200992887	200993003
ENSE00003667773	200992281	200992368
ENSE00003682054	201011392	201011472
ENSE00003789789	200997445	200997540
ENSE00003918392	200987365	200987532

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 96.42.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.2028 / max 289.5393, expressed in 1679 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
33197	9.2028	1679

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	96.42	gold quality
cerebellar vermis	UBERON:0004720	96.15	gold quality
Brodmann (1909) area 23	UBERON:0013554	94.30	gold quality
lateral nuclear group of thalamus	UBERON:0002736	93.88	gold quality
jejunal mucosa	UBERON:0000399	93.73	gold quality
Brodmann (1909) area 46	UBERON:0006483	93.06	gold quality
ileal mucosa	UBERON:0000331	90.46	gold quality
postcentral gyrus	UBERON:0002581	90.44	gold quality
oviduct epithelium	UBERON:0004804	90.41	gold quality
parietal lobe	UBERON:0001872	90.34	gold quality
pons	UBERON:0000988	89.94	gold quality
superior frontal gyrus	UBERON:0002661	89.56	gold quality
visceral pleura	UBERON:0002401	89.54	gold quality
nipple	UBERON:0002030	89.46	gold quality
occipital lobe	UBERON:0002021	89.42	gold quality
secondary oocyte	CL:0000655	89.27	gold quality
esophagus squamous epithelium	UBERON:0006920	89.16	gold quality
primary visual cortex	UBERON:0002436	89.08	gold quality
blood	UBERON:0000178	89.07	gold quality
bone marrow	UBERON:0002371	88.25	gold quality
upper leg skin	UBERON:0004262	88.20	gold quality
jejunum	UBERON:0002115	87.87	gold quality
entorhinal cortex	UBERON:0002728	87.87	gold quality
oral cavity	UBERON:0000167	87.80	gold quality
epithelial cell of pancreas	CL:0000083	87.55	gold quality
bone marrow cell	CL:0002092	87.45	gold quality
skin of hip	UBERON:0001554	87.29	gold quality
mucosa of sigmoid colon	UBERON:0004993	87.29	gold quality
colonic mucosa	UBERON:0000317	87.26	gold quality
mucosa of paranasal sinus	UBERON:0005030	87.20	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.40
E-CURD-97	no	630.40

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

499 targeting HYCC2, 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-8485	100.00	77.57	4731
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-9-5P	100.00	72.28	2361
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	hycc2	ENSDARG00000101696
		ENSDARG00000113433
mus_musculus	Hycc2	ENSMUSG00000038174
rattus_norvegicus	Hycc2	ENSRNOG00000025079
drosophila_melanogaster	Hyccin	FBGN0034269
caenorhabditis_elegans		WBGENE00017037

Paralogs (1): HYCC1 (ENSG00000122591)

Protein

Protein identifiers

Hyccin 2 — Q8IXS8 (reviewed: Q8IXS8)

All UniProt accessions (6): Q8IXS8, A0A804HIT6, C9J115, C9JNS4, C9JTA1, F8W7X4

UniProt curated annotations — full annotation on UniProt →

Function. Component of a complex required to localize phosphatidylinositol 4-kinase (PI4K) to the plasma membrane.

Subunit / interactions. Component of a phosphatidylinositol 4-kinase (PI4K) complex, composed of PI4KA, EFR3 (EFR3A or EFR3B), TTC7 (TTC7A or TTC7B) and HYCC (HYCC1 or HYCC2).

Subcellular location. Cytoplasm. Cytosol. Cell membrane.

Similarity. Belongs to the Hyccin family.

RefSeq proteins (12): NP_001308547, NP_001308548, NP_001308550, NP_001308551, NP_001308552, NP_001308553, NP_001308554, NP_001308555, NP_001308556, NP_001308557, NP_001308558, NP_776183 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR018619	Hyccin	Family

Pfam: PF09790

UniProt features (13 total): modified residue 8, region of interest 2, compositionally biased region 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IXS8-F1	69.27	0.42

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 (8): 442, 444, 491, 30, 306, 321, 341, 430

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 319 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLINOSITOL_METABOLIC_PROCESS, TGCACTT_MIR519C_MIR519B_MIR519A, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, TGACCTY_ERR1_Q2, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, GOBP_PHOSPHOLIPID_BIOSYNTHETIC_PROCESS, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, CATTTCA_MIR203, WANG_LMO4_TARGETS_DN, AGGAGTG_MIR483, GOBP_GLYCEROLIPID_BIOSYNTHETIC_PROCESS

GO Biological Process (2): phosphatidylinositol phosphate biosynthetic process (GO:0046854), protein localization to plasma membrane (GO:0072659)

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

GO Cellular Component (4): cytosol (GO:0005829), plasma membrane (GO:0005886), cytoplasm (GO:0005737), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
glycerophospholipid biosynthetic process	1
protein localization to membrane	1
protein localization to cell periphery	1
binding	1
cytoplasm	1
membrane	1
cell periphery	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

642 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HYCC2	TTC7A	Q9ULT0	673
HYCC2	EFR3A	Q14156	664
HYCC2	NIF3L1	Q9GZT8	649
HYCC2	PPIL3	Q9H2H8	616
HYCC2	EFR3B	Q9Y2G0	588
HYCC2	TTC7B	Q86TV6	565
HYCC2	KTI12	Q96EK9	521
HYCC2	PI4KA	P42356	502
HYCC2	CSE1L	P55060	492
HYCC2	BZW1	Q7L1Q6	479
HYCC2	ATOSB	Q7L5A3	429
HYCC2	NKPD1	Q17RQ9	428
HYCC2	NDUFB3	O43676	418
HYCC2	RGS9BP	Q6ZS82	407
HYCC2	LURAP1L	Q8IV03	405
HYCC2	AGFG1	P52594	405

IntAct

27 interactions, top by confidence:

A	B	Type	Score
HYCC2	TRIM27	psi-mi:“MI:0915”(physical association)	0.560
GOLGA2	HYCC2	psi-mi:“MI:0915”(physical association)	0.560
TRIM27	HYCC2	psi-mi:“MI:0915”(physical association)	0.560
HYCC2	GOLGA2	psi-mi:“MI:0915”(physical association)	0.560
MEOX1	HYCC2	psi-mi:“MI:0915”(physical association)	0.560
	HYCC2	psi-mi:“MI:0915”(physical association)	0.560
TTC7B	HYCC2	psi-mi:“MI:0915”(physical association)	0.560
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
HYCC2	DAPK1	psi-mi:“MI:0407”(direct interaction)	0.440
ENG	HYCC2	psi-mi:“MI:0407”(direct interaction)	0.440
DCAF4	IGLL5	psi-mi:“MI:0914”(association)	0.350
PI4KA	EFR3A	psi-mi:“MI:0914”(association)	0.350
CIMIP5	PI4KA	psi-mi:“MI:0914”(association)	0.350
CIMIP5	UNC119B	psi-mi:“MI:0914”(association)	0.350
	EBAG9	psi-mi:“MI:0914”(association)	0.350
KRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
HRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
CDH1	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
HYCC2		psi-mi:“MI:0915”(physical association)	0.000
TTC7B	HYCC2	psi-mi:“MI:0915”(physical association)	0.000
HYCC2	MEOX1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (22): FAM126B (Two-hybrid), FAM126B (Two-hybrid), FAM126B (Two-hybrid), FAM126B (Proximity Label-MS), FAM126B (Affinity Capture-MS), FAM126B (Reconstituted Complex), FAM126B (Affinity Capture-MS), FAM126B (Proximity Label-MS), FAM126B (Proximity Label-MS), FAM126B (Affinity Capture-MS), FAM126B (Two-hybrid), PDCL2 (Two-hybrid), TTC7B (Two-hybrid), FAM126B (Affinity Capture-RNA), FAM126B (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GUI7, A1DL98, A1L1K4, A4V8B4, A6QLJ4, A6ZMG4, A6ZR60, A7NVJ4, A9JR56, B3LLZ8, C5E1C7, C7GWA2, C8ZEW0, O13916, O60153, P0C2W9, P15130, P16135, P20486, P27271, P28974, P35198, P40063, P84395, Q04438, Q28EW5, Q28GG3, Q4V853, Q5FVD7, Q5R4F8, Q5R977, Q5RD94, Q5U550, Q66657, Q68EK9, Q68FR5, Q6AX78, Q6C3T0, Q751I6, Q7T2A3

Diamond homologs: Q5R977, Q5ZM13, Q6P121, Q6P9N1, Q8C729, Q8IXS8, Q9BYI3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	54
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2422 predictions. Top by Δscore:

Variant	Effect	Δscore
2:200988257:CTCA:C	donor_loss	1.0000
2:200988258:TCA:T	donor_loss	1.0000
2:200988259:CA:C	donor_loss	1.0000
2:200988260:A:AC	donor_gain	1.0000
2:200988260:A:AT	donor_loss	1.0000
2:200988260:AC:A	donor_gain	1.0000
2:200988260:ACCTT:A	donor_gain	1.0000
2:200988261:C:CA	donor_gain	1.0000
2:200988261:CC:C	donor_gain	1.0000
2:200988261:CCT:C	donor_gain	1.0000
2:200988261:CCTT:C	donor_gain	1.0000
2:200988261:CCTTC:C	donor_gain	1.0000
2:200988379:C:CT	acceptor_gain	1.0000
2:200988422:C:CC	acceptor_gain	1.0000
2:200988422:CTAC:C	acceptor_loss	1.0000
2:200988423:T:C	acceptor_loss	1.0000
2:200992274:AACTT:A	donor_loss	1.0000
2:200992275:ACTT:A	donor_loss	1.0000
2:200992276:CTTA:C	donor_loss	1.0000
2:200992277:TTA:T	donor_loss	1.0000
2:200992278:T:TG	donor_loss	1.0000
2:200992279:A:AC	donor_gain	1.0000
2:200992279:A:C	donor_loss	1.0000
2:200992280:C:CA	donor_loss	1.0000
2:200992280:C:CC	donor_gain	1.0000
2:200992881:A:AC	donor_gain	1.0000
2:200992882:C:CC	donor_gain	1.0000
2:200992882:CTTA:C	donor_gain	1.0000
2:200992885:A:AC	donor_gain	1.0000
2:200992886:C:CC	donor_gain	1.0000

AlphaMissense

3787 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:200988288:A:C	I322S	1.000
2:200988288:A:G	I322T	1.000
2:200988288:A:T	I322N	1.000
2:200988292:A:G	S321P	1.000
2:200988300:G:A	T318I	1.000
2:201009063:A:G	L147S	1.000
2:201011397:G:C	H137D	1.000
2:201011406:A:G	S134P	1.000
2:200988272:C:A	W327C	0.999
2:200988272:C:G	W327C	0.999
2:200988274:A:G	W327R	0.999
2:200988274:A:T	W327R	0.999
2:200988275:T:A	R326S	0.999
2:200988275:T:G	R326S	0.999
2:200988276:C:G	R326T	0.999
2:200988280:G:C	H325D	0.999
2:200988285:C:G	R323P	0.999
2:200988286:G:T	R323S	0.999
2:200988294:G:T	A320D	0.999
2:200988295:C:G	A320P	0.999
2:200988303:A:C	I317S	0.999
2:200988303:A:T	I317N	0.999
2:200988411:G:T	A281D	0.999
2:200988412:C:G	A281P	0.999
2:200992312:G:T	A267D	0.999
2:200992313:C:G	A267P	0.999
2:200997520:A:G	L184P	0.999
2:201009048:A:G	L152S	0.999
2:201011395:A:C	H137Q	0.999
2:201011395:A:T	H137Q	0.999

dbSNP variants (sampled 300 via entrez): RS1000006773 (2:201038882 C>A), RS1000043165 (2:201063890 A>C), RS1000071001 (2:201022742 GAAAGA>G), RS1000071148 (2:200990522 C>T), RS1000118307 (2:201046590 T>C), RS1000150711 (2:200994095 A>G), RS1000177138 (2:201043797 C>T), RS1000271703 (2:201018134 T>A), RS1000294071 (2:200997712 C>T), RS1000304768 (2:201004301 C>A,G,T), RS1000331112 (2:201050694 G>A), RS1000343375 (2:201015117 T>G), RS1000413051 (2:201010921 C>G,T), RS1000429158 (2:201007994 A>G), RS1000433628 (2:201059211 A>G,T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST003008_11	Triptolide cytotoxicity	3.000000e-07
GCST003008_16	Triptolide cytotoxicity	3.000000e-06
GCST003468_3	Chronic lymphocytic leukemia	3.000000e-08
GCST003842_21	Breast cancer (estrogen-receptor negative)	1.000000e-06
GCST003845_22	Breast cancer	7.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0006952	cytotoxicity measurement
EFO:0007664	outer ear morphology trait

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
Valproic Acid	decreases expression, decreases methylation, increases expression	2
Cyclosporine	increases expression	2
FR900359	affects phosphorylation	1
methylmercuric chloride	decreases expression	1
bisphenol A	affects cotreatment, decreases methylation	1
trichostatin A	affects expression	1
sodium arsenite	increases expression	1
di-n-butylphosphoric acid	affects expression	1
entinostat	decreases expression	1
K 7174	increases expression	1
abrine	increases expression	1
bisphenol S	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Leflunomide	increases expression	1
Benzo(a)pyrene	increases methylation	1
Caffeine	decreases phosphorylation	1
Cisplatin	affects cotreatment, decreases expression	1
Coumestrol	decreases expression	1
Dexamethasone	decreases expression, affects cotreatment	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	decreases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Methyl Methanesulfonate	increases expression	1
Dronabinol	increases expression	1
Thiram	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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