HECA

Summary

HECA (HECA ribonucleoprotein granule regulator, HGNC:21041) is a protein-coding gene on chromosome 6q24.1, encoding Headcase protein homolog (Q9UBI9). May play an important role in some human cancers.

This gene encodes the homolog of the Drosophila headcase protein, a highly basic, cytoplasmic protein that regulates the re-entry of imaginal cells into the mitotic cycle during adult morphogenesis. In Drosophila, the encoded protein also inhibits terminal branching of neighboring cells during tracheal development.

Source: NCBI Gene 51696 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 54 total
• Phenotypes (HPO): 9
• MANE Select transcript: NM_016217

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21041
Approved symbol	HECA
Name	HECA ribonucleoprotein granule regulator
Location	6q24.1
Locus type	gene with protein product
Status	Approved
Aliases	HDCL, hHDC, HDC, dJ225E12.1
Ensembl gene	ENSG00000112406
Ensembl biotype	protein_coding
OMIM	607977
Entrez	51696

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000367658, ENST00000958322, ENST00000958323

RefSeq mRNA: 1 — MANE Select: NM_016217 NM_016217

CCDS: CCDS5194

Canonical transcript exons

ENST00000367658 — 4 exons

Exon	Start	End
ENSE00000764763	139166284	139167324
ENSE00000764764	139174385	139174539
ENSE00001445282	139176941	139180802
ENSE00001445283	139135080	139135667

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 99.05.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 30.1438 / max 739.3179, expressed in 1773 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
70135	24.2120	1756
70134	5.9318	1567

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
amniotic fluid	UBERON:0000173	99.05	gold quality
upper leg skin	UBERON:0004262	97.30	gold quality
jejunal mucosa	UBERON:0000399	95.84	gold quality
skin of hip	UBERON:0001554	95.83	gold quality
esophagus squamous epithelium	UBERON:0006920	95.71	gold quality
epithelium of nasopharynx	UBERON:0001951	95.65	gold quality
hair follicle	UBERON:0002073	94.88	gold quality
cartilage tissue	UBERON:0002418	94.83	gold quality
squamous epithelium	UBERON:0006914	94.78	gold quality
lower lobe of lung	UBERON:0008949	94.66	gold quality
superficial temporal artery	UBERON:0001614	94.52	gold quality
gingiva	UBERON:0001828	94.35	gold quality
gingival epithelium	UBERON:0001949	94.34	gold quality
oviduct epithelium	UBERON:0004804	94.09	gold quality
epithelium of esophagus	UBERON:0001976	93.98	gold quality
oral cavity	UBERON:0000167	93.88	gold quality
ileal mucosa	UBERON:0000331	93.79	gold quality
thymus	UBERON:0002370	93.46	gold quality
upper arm skin	UBERON:0004263	93.37	gold quality
pleura	UBERON:0000977	93.32	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	93.22	gold quality
tendon of biceps brachii	UBERON:0008188	93.22	gold quality
parietal pleura	UBERON:0002400	93.18	gold quality
visceral pleura	UBERON:0002401	93.16	gold quality
jejunum	UBERON:0002115	93.12	gold quality
buccal mucosa cell	CL:0002336	93.03	gold quality
parotid gland	UBERON:0001831	92.96	gold quality
germinal epithelium of ovary	UBERON:0001304	92.72	gold quality
cervix squamous epithelium	UBERON:0006922	92.67	silver quality
blood	UBERON:0000178	92.60	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-100618	no	500.21
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TCF4, TCF7L2

miRNA regulators (miRDB)

227 targeting HECA, 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-3163	100.00	77.23	8605
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-607	99.97	73.62	5593

Literature-anchored findings (GeneRIF, showing 5)

• Data show that HECA may be an early-stage classifier of colorectal cancer that can discriminate between late- and early-stage disease. (PMID:16525680)
• Human HECA slows down cell division of oral squamous cell carcinoma cells and may therefore act as a tumor suppressor in head and neck cancer. (PMID:19643820)
• HECA expression is markedly decreased in oral squamous cell carcinoma (OSCC) compared to controls and is associated with decreased sensitivity to cisplatin in OSCC cell lines (PMID:22100912)
• Mutational and expressional alterations of a candidate tumor suppressor HECA gene in gastric and colorectal cancers. (PMID:32088090)
• Functional analysis of HECA variants identified in congenital heart disease in the Chinese population. (PMID:35949005)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	heca	ENSDARG00000042877
mus_musculus	Heca	ENSMUSG00000039879
rattus_norvegicus	Heca	ENSRNOG00000060972
drosophila_melanogaster	heca	FBGN0010113
caenorhabditis_elegans	cri-1	WBGENE00010614
caenorhabditis_elegans		WBGENE00015073

Protein

Protein identifiers

Headcase protein homolog — Q9UBI9 (reviewed: Q9UBI9)

All UniProt accessions (1): Q9UBI9

UniProt curated annotations — full annotation on UniProt →

Function. May play an important role in some human cancers. May be part of the regulatory mechanism in the development of epithelial tube networks such as the circulatory system and lungs.

Tissue specificity. Expressed in all tissues examined. Highest levels are in the spleen, thymus, peripheral blood and heart. Lowest in the kidney and pancreas.

RefSeq proteins (1): NP_057301* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026066	Headcase	Family
IPR031947	Headcase_mid	Domain
IPR054537	HECA_N	Domain

Pfam: PF15353, PF16002

UniProt features (7 total): region of interest 2, compositionally biased region 2, modified residue 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UBI9-F1	68.78	0.30

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 (2): 264, 268

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 392 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_DN, GOBP_PHENOL_CONTAINING_COMPOUND_METABOLIC_PROCESS, LEE_NEURAL_CREST_STEM_CELL_DN, TAATAAT_MIR126, GOBP_PHENOL_CONTAINING_COMPOUND_BIOSYNTHETIC_PROCESS, GNF2_CASP8, TGCACTT_MIR519C_MIR519B_MIR519A, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, MATTIOLI_MGUS_VS_PCL, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, KEGG_HISTIDINE_METABOLISM, FOSTER_TOLERANT_MACROPHAGE_UP, MARTINEZ_RB1_TARGETS_DN, RAMALHO_STEMNESS_DN, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE

GO Biological Process (2): respiratory tube development (GO:0030323), negative regulation of mitotic cell cycle (GO:0045930)

GO Molecular Function (0):

GO Cellular Component (3): nucleus (GO:0005634), cytoplasm (GO:0005737), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
tube development	1
animal organ development	1
mitotic cell cycle	1
regulation of mitotic cell cycle	1
negative regulation of cell cycle	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

484 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HECA	SELE	P16111	862
HECA	SNX20	Q7Z614	848
HECA	SELPLG	Q14242	821
HECA	FUT7	Q11130	820
HECA	SELP	P16109	777
HECA	PLEKHB1	Q9UF11	596
HECA	SELL	P14151	573
HECA	SPN	P16150	519
HECA	CHST4	Q8NCG5	505
HECA	GCNT1	Q02742	480
HECA	NTAN1	Q96AB6	475
HECA	OSGEP	Q9NPF4	454
HECA	GP1BA	P07359	434
HECA	CCNL2	Q96S94	411
HECA	CCR7	P32248	404

IntAct

2 interactions, top by confidence:

A	B	Type	Score
CACNA1C	SYT5	psi-mi:“MI:0914”(association)	0.350

BioGRID (13): HECA (Affinity Capture-MS), HECA (Proximity Label-MS), HECA (Proximity Label-MS), HECA (Proximity Label-MS), HECA (Proximity Label-MS), HECA (Proximity Label-MS), HECA (Negative Genetic), HECA (Affinity Capture-MS), HECA (Affinity Capture-MS), HECA (Affinity Capture-MS), HECA (Proximity Label-MS), HECA (Cross-Linking-MS (XL-MS)), HECA (Affinity Capture-RNA)

ESM2 similar proteins: A1L1C7, O08873, O42611, O60716, O94776, O94967, P83094, Q01826, Q0P5J8, Q15542, Q3UHE1, Q3UVG3, Q4R8N2, Q58A45, Q5EY87, Q5JSJ4, Q5M7R9, Q5R7S4, Q5RAR8, Q5TKA1, Q60611, Q640Q5, Q658Y4, Q68FH0, Q6ISB3, Q6NT76, Q6TEP1, Q80U28, Q8BIE6, Q8BJA3, Q8C092, Q8C0V0, Q8C735, Q8C8N2, Q8CGF6, Q8K5C0, Q8N9R8, Q8VI24, Q8WXG6, Q90ZY6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	49
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3181 predictions. Top by Δscore:

Variant	Effect	Δscore
15:50243243:CC:C	acceptor_gain	1.0000
15:50243244:CC:C	acceptor_gain	1.0000
15:50248244:CATGT:C	donor_gain	1.0000
15:50252425:CTCA:C	donor_loss	1.0000
15:50252426:TCA:T	donor_loss	1.0000
15:50252427:CACCA:C	donor_loss	1.0000
15:50252428:A:AC	donor_gain	1.0000
15:50252428:AC:A	donor_gain	1.0000
15:50252428:ACCAT:A	donor_loss	1.0000
15:50252429:C:CC	donor_gain	1.0000
15:50252429:CC:C	donor_gain	1.0000
15:50252518:ACCC:A	acceptor_loss	1.0000
15:50252519:CC:C	acceptor_gain	1.0000
15:50252519:CCCT:C	acceptor_loss	1.0000
15:50252520:CC:C	acceptor_gain	1.0000
15:50252520:CCTGT:C	acceptor_loss	1.0000
15:50252521:C:CC	acceptor_gain	1.0000
15:50252522:T:G	acceptor_loss	1.0000
15:50253662:CAGAC:C	acceptor_gain	1.0000
15:50253666:CCTAG:C	acceptor_loss	1.0000
15:50253667:CT:C	acceptor_loss	1.0000
15:50254128:A:AC	donor_gain	1.0000
15:50254129:C:CC	donor_gain	1.0000
15:50254161:T:TA	donor_gain	1.0000
15:50254269:TGAGC:T	acceptor_gain	1.0000
15:50254272:GCCTA:G	acceptor_loss	1.0000
15:50254274:C:A	acceptor_loss	1.0000
15:50254274:C:CC	acceptor_gain	1.0000
15:50254275:T:A	acceptor_loss	1.0000
15:50254527:CA:C	donor_loss	1.0000

AlphaMissense

3596 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:139166364:T:A	C118S	1.000
6:139166364:T:C	C118R	1.000
6:139166365:G:A	C118Y	1.000
6:139166365:G:C	C118S	1.000
6:139166366:C:G	C118W	1.000
6:139166409:T:C	C133R	1.000
6:139166411:C:G	C133W	1.000
6:139166421:T:A	W137R	1.000
6:139166421:T:C	W137R	1.000
6:139166423:G:C	W137C	1.000
6:139166423:G:T	W137C	1.000
6:139166437:T:C	L142P	1.000
6:139166446:T:C	F145S	1.000
6:139166458:G:A	G149D	1.000
6:139166460:C:A	R150S	1.000
6:139166464:C:A	A151E	1.000
6:139166466:C:A	R152S	1.000
6:139166469:A:C	S153R	1.000
6:139166471:C:A	S153R	1.000
6:139166471:C:G	S153R	1.000
6:139166472:T:A	W154R	1.000
6:139166472:T:C	W154R	1.000
6:139166473:G:C	W154S	1.000
6:139166474:G:C	W154C	1.000
6:139166474:G:T	W154C	1.000
6:139166486:A:C	Q158H	1.000
6:139166486:A:T	Q158H	1.000
6:139166494:A:C	Q161P	1.000
6:139166496:A:G	N162D	1.000
6:139166498:C:A	N162K	1.000

dbSNP variants (sampled 300 via entrez): RS1000040893 (6:139170304 C>G,T), RS1000054403 (6:139177312 G>A,C,T), RS1000112450 (6:139168793 T>C), RS1000190101 (6:139164320 G>A), RS1000240675 (6:139171375 T>C), RS1000382796 (6:139134447 G>A), RS1000424672 (6:139178547 T>C), RS1000451327 (6:139154432 G>A), RS1000457733 (6:139158802 A>G), RS1000514904 (6:139134395 CTTTTCTTTTTT>C), RS1000538843 (6:139165629 T>G), RS1000587222 (6:139178767 C>T), RS1000726316 (6:139164930 T>A,C), RS1000753114 (6:139141585 G>A), RS1000862737 (6:139146287 A>G,T)

Disease associations

OMIM: gene MIM:607977 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

9 total (9 of 9 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000718	Aggressive behavior
HP:0000722	Compulsive behaviors
HP:0000742	Self-mutilation
HP:0002360	Sleep disturbance
HP:0007018	Attention deficit hyperactivity disorder
HP:0010529	Echolalia
HP:0100034	Motor tics
HP:0100035	Phonic tics

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST005956_33	Waist-to-hip ratio adjusted for BMI	6.000000e-09
GCST005962_46	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	6.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs17740607	HDC		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	6
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	increases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
trichostatin A	increases expression	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
zinc chromate	increases abundance, increases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
epigallocatechin gallate	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	increases expression, increases abundance	1
perfluorooctane sulfonic acid	decreases expression	1
ICG 001	decreases 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
Sunitinib	increases expression	1
Arsenic Trioxide	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Estradiol	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Methyl Methanesulfonate	increases expression	1
Ozone	affects expression, increases abundance	1
Phenobarbital	affects expression	1
Silicon Dioxide	decreases expression	1

Clinical trials (associated diseases)

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