EVA1C

Summary

EVA1C (eva-1 homolog C, HGNC:13239) is a protein-coding gene on chromosome 21q22.11, encoding Protein eva-1 homolog C (P58658). Binds heparin.

Enables heparin binding activity. Located in extracellular region.

Source: NCBI Gene 59271 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 74 total
• MANE Select transcript: NM_058187

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13239
Approved symbol	EVA1C
Name	eva-1 homolog C
Location	21q22.11
Locus type	gene with protein product
Status	Approved
Aliases	B18, PRED34, B19
Ensembl gene	ENSG00000166979
Ensembl biotype	protein_coding
Entrez	59271

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 21 protein_coding, 4 protein_coding_CDS_not_defined, 3 nonsense_mediated_decay, 2 retained_intron

ENST00000300255, ENST00000382699, ENST00000401402, ENST00000412833, ENST00000435323, ENST00000437338, ENST00000457807, ENST00000459833, ENST00000464037, ENST00000469079, ENST00000481638, ENST00000485488, ENST00000496615, ENST00000898243, ENST00000898244, ENST00000898245, ENST00000898246, ENST00000898247, ENST00000898248, ENST00000898249, ENST00000898250, ENST00000898251, ENST00000898252, ENST00000898253, ENST00000898254, ENST00000960932, ENST00000960933, ENST00000960934, ENST00000960935, ENST00000960936

RefSeq mRNA: 4 — MANE Select: NM_058187 NM_001286556, NM_001320744, NM_001320745, NM_058187

CCDS: CCDS13614, CCDS68186

Canonical transcript exons

ENST00000300255 — 8 exons

Exon	Start	End
ENSE00001840809	32412706	32413013
ENSE00003488598	32503926	32504015
ENSE00003516969	32501415	32501495
ENSE00003528501	32453312	32453508
ENSE00003593323	32457597	32457720
ENSE00003610773	32467696	32467848
ENSE00003640508	32495027	32495170
ENSE00003843039	32514814	32515387

Expression profiles

Bgee: expression breadth ubiquitous, 239 present calls, max score 97.00.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.0898 / max 145.7123, expressed in 1291 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
188821	2.4416	758
188817	0.9297	548
188813	0.8965	531
188814	0.8855	480
188819	0.8291	457
188822	0.6433	331
188815	0.5282	266
188816	0.4714	102
188818	0.1818	66
188820	0.1313	54

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
olfactory segment of nasal mucosa	UBERON:0005386	97.00	gold quality
left uterine tube	UBERON:0001303	96.78	gold quality
mucosa of stomach	UBERON:0001199	96.72	gold quality
right uterine tube	UBERON:0001302	96.22	gold quality
body of uterus	UBERON:0009853	95.54	gold quality
parietal pleura	UBERON:0002400	95.53	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.19	gold quality
pancreatic ductal cell	CL:0002079	95.15	silver quality
decidua	UBERON:0002450	95.09	gold quality
tibial nerve	UBERON:0001323	95.01	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.01	gold quality
lower esophagus	UBERON:0013473	94.97	gold quality
omental fat pad	UBERON:0010414	94.94	gold quality
peritoneum	UBERON:0002358	94.92	gold quality
palpebral conjunctiva	UBERON:0001812	94.44	gold quality
ascending aorta	UBERON:0001496	94.39	gold quality
thoracic aorta	UBERON:0001515	94.37	gold quality
skin of leg	UBERON:0001511	94.33	gold quality
descending thoracic aorta	UBERON:0002345	94.12	gold quality
ectocervix	UBERON:0012249	94.12	gold quality
right lung	UBERON:0002167	94.11	gold quality
endocervix	UBERON:0000458	93.97	gold quality
adipose tissue of abdominal region	UBERON:0007808	93.94	gold quality
skin of abdomen	UBERON:0001416	93.93	gold quality
prostate gland	UBERON:0002367	93.90	gold quality
upper lobe of left lung	UBERON:0008952	93.84	gold quality
bronchial epithelial cell	CL:0002328	93.76	gold quality
sural nerve	UBERON:0015488	93.75	gold quality
left ovary	UBERON:0002119	93.63	gold quality
aorta	UBERON:0000947	93.32	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	21.68

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

20 targeting EVA1C, 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-4713-3P	100.00	65.92	505
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-205-5P	99.81	70.05	1557
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-6832-3P	99.52	70.44	1726
HSA-MIR-4667-3P	99.26	65.45	1608
HSA-MIR-376A-3P	99.06	69.17	1128
HSA-MIR-376B-3P	99.06	69.17	1128
HSA-MIR-3154	98.94	66.55	1455
HSA-MIR-423-5P	98.69	67.48	1522
HSA-MIR-6868-3P	98.63	69.64	2259
HSA-MIR-3184-5P	98.56	67.13	1491
HSA-MIR-1248	98.47	67.54	1314
HSA-MIR-125A-3P	97.04	66.92	902
HSA-MIR-552-3P	96.68	64.12	1026

Literature-anchored findings (GeneRIF, showing 3)

• validated occurrence of an unusual TG 3’ splice site in intron 3 (PMID:17672918)
• C21orf63 is a heparin-binding protein; in glycan microassay, the product of C21orf63 binds with heparin and heparan sulfate; real-time polymerase chain reaction and tissue immunostaining imply that C21orf63 is expressed on epithelia of various tissues (PMID:19470522)
• EVA1C Is a Potential Prognostic Biomarker and Correlated With Immune Infiltration Levels in WHO Grade II/III Glioma. (PMID:34267752)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	eva1c	ENSDARG00000056024
mus_musculus	Eva1c	ENSMUSG00000039903
rattus_norvegicus	Eva1c	ENSRNOG00000002072
drosophila_melanogaster	mthl14	FBGN0052476
caenorhabditis_elegans		WBGENE00017948

Paralogs (42): CALCR (ENSG00000004948), GIPR (ENSG00000010310), ADGRA2 (ENSG00000020181), CALCRL (ENSG00000064989), GLP2R (ENSG00000065325), ADGRF5 (ENSG00000069122), ADGRL1 (ENSG00000072071), ADCYAP1R1 (ENSG00000078549), SCTR (ENSG00000080293), VIPR2 (ENSG00000106018), CRHR2 (ENSG00000106113), GHRHR (ENSG00000106128), ADGRD1 (ENSG00000111452), GLP1R (ENSG00000112164), ADGRG6 (ENSG00000112414), VIPR1 (ENSG00000114812), ADGRL2 (ENSG00000117114), CRHR1 (ENSG00000120088), ADGRB2 (ENSG00000121753), ADGRE5 (ENSG00000123146), ADGRE2 (ENSG00000127507), ADGRE3 (ENSG00000131355), ADGRB3 (ENSG00000135298), PTH2R (ENSG00000144407), ADGRG7 (ENSG00000144820), ADGRL3 (ENSG00000150471), ADGRA3 (ENSG00000152990), ADGRF1 (ENSG00000153292), ADGRF4 (ENSG00000153294), ADGRG4 (ENSG00000156920), ADGRG5 (ENSG00000159618), PTH1R (ENSG00000160801), ADGRL4 (ENSG00000162618), ADGRF3 (ENSG00000173567), ADGRG2 (ENSG00000173698), ADGRE1 (ENSG00000174837), ADGRD2 (ENSG00000180264), ADGRB1 (ENSG00000181790), ADGRG3 (ENSG00000182885), ADGRA1 (ENSG00000197177)

Protein

Protein identifiers

Protein eva-1 homolog C — P58658 (reviewed: P58658)

Alternative names: Protein FAM176C, SUE21

All UniProt accessions (5): P58658, A0A0C4DG64, B5MC74, C9JS02, F8WEK6

UniProt curated annotations — full annotation on UniProt →

Function. Binds heparin.

Subcellular location. Membrane.

Tissue specificity. Ubiquitous.

Similarity. Belongs to the EVA1 family.

Isoforms (3)

UniProt ID	Names	Canonical?
P58658-1	1	yes
P58658-2	2
P58658-3	3

RefSeq proteins (4): NP_001273485, NP_001307673, NP_001307674, NP_478067* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000922	Lectin_gal-bd_dom	Domain
IPR039500	EVA1_dom	Domain
IPR043159	Lectin_gal-bd_sf	Homologous_superfamily

Pfam: PF02140, PF14851

UniProt features (17 total): splice variant 3, glycosylation site 2, sequence conflict 2, topological domain 2, domain 2, region of interest 2, signal peptide 1, chain 1, transmembrane region 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P58658-F1	70.39	0.28

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Glycosylation sites (2): 62, 165

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 119 (showing top): BENPORATH_ES_WITH_H3K27ME3, SP3_Q3, SCHLESINGER_METHYLATED_DE_NOVO_IN_CANCER, CHANDRAN_METASTASIS_DN, SRF_Q5_01, SRF_C, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, GRE_C, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP, OCT1_06, AAAGGGA_MIR204_MIR211, TGACATY_UNKNOWN, GATA1_03, GOMF_GLYCOSAMINOGLYCAN_BINDING, NAKAMURA_TUMOR_ZONE_PERIPHERAL_VS_CENTRAL_DN

GO Biological Process (0):

GO Molecular Function (2): heparin binding (GO:0008201), carbohydrate binding (GO:0030246)

GO Cellular Component (2): membrane (GO:0016020), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
glycosaminoglycan binding	1
sulfur compound binding	1
binding	1

Protein interactions and networks

STRING

672 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EVA1C	URB1	O60287	587
EVA1C	POFUT2	Q9Y2G5	587
EVA1C	DONSON	Q9NYP3	582
EVA1C	HEMK2	Q9Y5N5	576
EVA1C	PDXK	O00764	489
EVA1C	DOP1B	Q9Y3R5	471
EVA1C	PAXBP1	Q9Y5B6	471
EVA1C	RCAN1	P53805	440
EVA1C	YBEY	P58557	437
EVA1C	MCHR2	Q969V1	419
EVA1C	ITSN1	Q15811	415
EVA1C	HUNK	P57058	412
EVA1C	CCDC152	Q4G0S7	412
EVA1C	MPZL2	O60487	400
EVA1C	PYURF	Q96I23	399

IntAct

9 interactions, top by confidence:

A	B	Type	Score
EVA1C	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
DBF4B	CDC7	psi-mi:“MI:0914”(association)	0.530
EVA1C	STK25	psi-mi:“MI:0914”(association)	0.530
DBF4B	CDC7	psi-mi:“MI:0914”(association)	0.350
rep	GPR89A	psi-mi:“MI:0914”(association)	0.350
EVA1C		psi-mi:“MI:0915”(physical association)	0.000

BioGRID (115): ATP2A3 (Affinity Capture-MS), TMEM192 (Affinity Capture-MS), POM121 (Affinity Capture-MS), TBL2 (Affinity Capture-MS), SACM1L (Affinity Capture-MS), RETSAT (Affinity Capture-MS), PNPLA6 (Affinity Capture-MS), DHRS7 (Affinity Capture-MS), SPTLC2 (Affinity Capture-MS), NRP1 (Affinity Capture-MS), CYP51A1 (Affinity Capture-MS), CTDNEP1 (Affinity Capture-MS), KIDINS220 (Affinity Capture-MS), PNMA2 (Affinity Capture-MS), TYW1 (Affinity Capture-MS)

ESM2 similar proteins: A6NCL2, D3ZTT2, O19131, O46655, O70280, P01177, P01178, P01179, P01180, P01183, P01185, P01186, P03973, P13389, P19438, P22298, P22934, P25118, P35454, P35455, P50555, P58658, P58659, Q02509, Q14AE4, Q32LD3, Q3URS3, Q5T700, Q68US5, Q6UWE3, Q6UWL2, Q6V9X0, Q6WN34, Q76LW6, Q86Y78, Q8BPP5, Q8BVP6, Q8N6Q3, Q8VEA6, Q8WXA2

Diamond homologs: A2BD09, A4IIT5, A6QLD2, A6QLU6, B0BNI5, B5MFE9, B7ZCC9, C0HK23, C0HK24, O70624, O88917, O88923, O88998, O94910, O95490, O95838, O95897, O97817, O97827, O97831, P22031, P32215, P35464, P43219, P48960, P58658, P58659, P63056, P63057, P70205, P86177, P86178, P86179, Q14246, Q29627, Q2PT31, Q2Q421, Q2Q426, Q3UZZ4, Q3V1G4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	59
Likely benign	3
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

1611 predictions. Top by Δscore:

Variant	Effect	Δscore
21:32456819:C:G	donor_gain	1.0000
21:32457679:G:GT	donor_gain	1.0000
21:32457716:ACCTA:A	donor_gain	1.0000
21:32457717:CCTA:C	donor_gain	1.0000
21:32457718:CTA:C	donor_gain	1.0000
21:32457719:TA:T	donor_gain	1.0000
21:32457721:G:GG	donor_gain	1.0000
21:32467688:T:TA	acceptor_gain	1.0000
21:32467693:CAGAT:C	acceptor_loss	1.0000
21:32467694:A:AG	acceptor_gain	1.0000
21:32467694:A:T	acceptor_loss	1.0000
21:32467694:AGAT:A	acceptor_gain	1.0000
21:32467695:G:GG	acceptor_gain	1.0000
21:32467695:GA:G	acceptor_gain	1.0000
21:32467695:GAT:G	acceptor_gain	1.0000
21:32467695:GATG:G	acceptor_gain	1.0000
21:32467695:GATGA:G	acceptor_gain	1.0000
21:32467804:A:T	donor_gain	1.0000
21:32467845:TTCGG:T	donor_loss	1.0000
21:32467846:TCGGT:T	donor_loss	1.0000
21:32467847:CGG:C	donor_loss	1.0000
21:32467848:GGTA:G	donor_loss	1.0000
21:32467849:G:GG	donor_gain	1.0000
21:32467849:G:T	donor_loss	1.0000
21:32467850:T:A	donor_loss	1.0000
21:32501413:A:AG	acceptor_gain	1.0000
21:32501414:G:GG	acceptor_gain	1.0000
21:32514809:TGCA:T	acceptor_loss	1.0000
21:32514810:GCAG:G	acceptor_loss	1.0000
21:32514811:CAGC:C	acceptor_loss	1.0000

AlphaMissense

2885 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
21:32453380:T:A	C77S	0.999
21:32453380:T:C	C77R	0.999
21:32453381:G:C	C77S	0.999
21:32457711:T:A	C158S	0.999
21:32457711:T:C	C158R	0.999
21:32457712:G:C	C158S	0.999
21:32453382:C:G	C77W	0.998
21:32453405:T:A	V85D	0.998
21:32457612:T:A	C125S	0.998
21:32457612:T:C	C125R	0.998
21:32457613:G:C	C125S	0.998
21:32457694:T:C	L152P	0.998
21:32457713:C:G	C158W	0.998
21:32453381:G:A	C77Y	0.997
21:32457614:C:G	C125W	0.997
21:32457700:T:A	V154D	0.997
21:32457712:G:A	C158Y	0.997
21:32457712:G:T	C158F	0.997
21:32453399:T:A	I83K	0.996
21:32457630:T:A	C131S	0.996
21:32457630:T:C	C131R	0.996
21:32457631:G:A	C131Y	0.996
21:32457631:G:C	C131S	0.996
21:32457632:C:G	C131W	0.996
21:32457643:T:A	V135D	0.996
21:32457658:T:G	F140C	0.996
21:32514849:A:C	S329R	0.996
21:32514851:T:A	S329R	0.996
21:32514851:T:G	S329R	0.996
21:32453381:G:T	C77F	0.995

dbSNP variants (sampled 300 via entrez): RS1000012484 (21:32420207 T>C), RS1000027786 (21:32499484 G>A), RS1000029428 (21:32488809 C>T), RS1000070224 (21:32473626 C>T), RS1000122376 (21:32432745 G>A), RS1000136123 (21:32482560 G>A), RS1000142729 (21:32495521 G>A), RS1000157273 (21:32435464 C>T), RS1000204863 (21:32481595 A>G), RS1000231476 (21:32414190 A>G), RS1000372037 (21:32469239 C>G), RS1000392317 (21:32515857 C>T), RS1000439816 (21:32499105 T>C), RS1000484284 (21:32427265 G>A), RS1000494465 (21:32494545 G>A)

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

10 associations (top):

Study	Trait	p-value
GCST006585_100	Blood protein levels	2.000000e-12
GCST007095_24	Systolic blood pressure	9.000000e-06
GCST007095_25	Systolic blood pressure	2.000000e-06
GCST007096_208	Pulse pressure	6.000000e-08
GCST007097_29	Pulse pressure	2.000000e-07
GCST007097_30	Pulse pressure	3.000000e-06
GCST007099_27	Systolic blood pressure	3.000000e-07
GCST012287_1	Hepatitis B virus-related hepatocellular carcinoma vs chronic hepatitis B infection	2.000000e-06
GCST012484_22	Cerebral amyloid angiopathy x APOEe4 status interaction in Alzheimer’s disease	8.000000e-06
GCST90013407_175	Liver enzyme levels (gamma-glutamyl transferase)	1.000000e-09

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0006335	systolic blood pressure
EFO:0005763	pulse pressure measurement
EFO:0008505	hepatitis virus-related hepatocellular carcinoma
EFO:0007659	APOE carrier status
EFO:0004532	serum gamma-glutamyl transferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases expression, affects methylation	3
Particulate Matter	decreases expression, increases abundance	2
bisphenol A	decreases methylation	1
terbufos	increases methylation	1
tris(2-butoxyethyl) phosphate	affects expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
benzo(e)pyrene	increases methylation	1
nickel sulfate	increases expression	1
di-n-butylphosphoric acid	affects expression	1
abrine	decreases expression	1
NSC 689534	affects binding, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Temozolomide	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Cisplatin	increases expression	1
Copper	affects binding, decreases expression	1
Dexamethasone	increases expression	1
Doxorubicin	decreases expression	1
Fonofos	increases methylation	1
Estradiol	affects cotreatment, decreases expression	1
Methapyrilene	increases methylation	1
Parathion	increases methylation	1
Testosterone	decreases expression	1
Thiram	decreases expression	1
Valproic Acid	decreases methylation	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Antirheumatic Agents	decreases expression	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

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