HMCN1

Summary

HMCN1 (hemicentin 1, HGNC:19194) is a protein-coding gene on chromosome 1q25.3-q31.1, encoding Hemicentin-1 (Q96RW7). Involved in transforming growth factor beta-mediated rearrangement of the podocyte cytoskeleton which includes reduction of F-actin fibers and broadening, flattening and elongation of podocytes.

This gene encodes a large extracellular member of the immunoglobulin superfamily. A similar protein in C. elegans forms long, fine tracks at specific extracellular sites that are involved in many processes such as stabilization of the germline syncytium, anchorage of mechanosensory neurons to the epidermis, and organization of hemidesmosomes in the epidermis. Mutations in this gene may be associated with age-related macular degeneration.

Source: NCBI Gene 83872 — RefSeq curated summary.

At a glance

• Gene–disease (curated): age related macular degeneration 1 (Limited, GenCC)
• GWAS associations: 5
• Clinical variants (ClinVar): 3,862 total — 1 pathogenic
• Phenotypes (HPO): 9
• MANE Select transcript: NM_031935

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19194
Approved symbol	HMCN1
Name	hemicentin 1
Location	1q25.3-q31.1
Locus type	gene with protein product
Status	Approved
Aliases	FBLN6, FIBL6, FIBL-6
Ensembl gene	ENSG00000143341
Ensembl biotype	protein_coding
OMIM	608548
Entrez	83872

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding_CDS_not_defined, 2 protein_coding

ENST00000271588, ENST00000414277, ENST00000475585, ENST00000485744, ENST00000493413

RefSeq mRNA: 1 — MANE Select: NM_031935 NM_031935

CCDS: CCDS30956

Canonical transcript exons

ENST00000271588 — 107 exons

Exon	Start	End
ENSE00000823001	185962518	185962659
ENSE00000959352	186086246	186086407
ENSE00000959377	186128078	186128291
ENSE00000959387	186145753	186145923
ENSE00000959388	186151200	186151349
ENSE00000959389	186151606	186151743
ENSE00000959390	186152750	186152871
ENSE00000959391	186153750	186153987
ENSE00000959392	186165111	186165173
ENSE00000959393	186166184	186166303
ENSE00000959396	186172006	186172131
ENSE00000959397	186174514	186174642
ENSE00000959398	186178416	186178766
ENSE00000959403	186187883	186188009
ENSE00000959406	186166808	186166942
ENSE00000959408	186182168	186182287
ENSE00001068036	186052952	186053074
ENSE00001068037	185997429	185997524
ENSE00001068038	186053825	186053986
ENSE00001068044	185864470	185864628
ENSE00001068045	186055393	186055674
ENSE00001068046	186041013	186041136
ENSE00001068048	185925047	185925191
ENSE00001068053	185865741	185865863
ENSE00001068056	186061851	186061964
ENSE00001068060	185923390	185923653
ENSE00001068062	186039728	186039879
ENSE00001068064	186015159	186015437
ENSE00001068066	185911674	185911780
ENSE00001068071	186074741	186074891
ENSE00001068072	186057234	186057401
ENSE00001068073	186001298	186001428
ENSE00001068074	186038829	186039005
ENSE00001068075	185734391	185735047
ENSE00001068076	186082865	186082961
ENSE00001068077	186023030	186023153
ENSE00001068078	186019541	186019695
ENSE00001068079	186037934	186038035
ENSE00001068081	186001594	186001741
ENSE00001068082	185933549	185933824
ENSE00001068087	186081207	186081394
ENSE00001068088	185993182	185993309
ENSE00001068090	186048743	186048839
ENSE00001068179	186018183	186018352
ENSE00001068182	185909337	185909508
ENSE00001068183	185928546	185928667
ENSE00001068187	186045688	186045863
ENSE00001068188	186007128	186007282
ENSE00001068189	186067834	186068007
ENSE00001068191	185846026	185846096
ENSE00001068192	186062514	186062600
ENSE00001068193	186003718	186003844
ENSE00001068194	186016963	186017071
ENSE00001068195	186076428	186076622
ENSE00001068196	186015958	186016239
ENSE00001068197	185922379	185922499
ENSE00001068202	186078107	186078220
ENSE00001068203	185994815	185995087
ENSE00001068204	186065238	186065429
ENSE00001068205	186000045	186000239
ENSE00001068206	186069663	186069776
ENSE00001126777	186144173	186144343
ENSE00001126799	186137498	186137668
ENSE00001126807	186136668	186136937
ENSE00001126815	186130507	186130697
ENSE00001126835	186122951	186123220
ENSE00001126855	186119191	186119298
ENSE00001126863	186117459	186117623
ENSE00001126868	186116994	186117115
ENSE00001126872	186115258	186115414
ENSE00001126879	186114819	186114946
ENSE00001126883	186113979	186114123
ENSE00001127063	186145403	186145573
ENSE00001252237	186137802	186137972
ENSE00001252265	186132328	186132409
ENSE00001252284	186129966	186130100
ENSE00001361964	186144533	186144703
ENSE00001362005	186125604	186125794
ENSE00001362013	186120011	186120145
ENSE00001362017	186119745	186119882
ENSE00001362041	186112812	186112953
ENSE00001362043	186108461	186108597
ENSE00001362046	186106884	186106965
ENSE00001362049	186103472	186103668
ENSE00001403973	186088606	186088755
ENSE00001405011	186093134	186093258
ENSE00001405537	186088145	186088276
ENSE00001406542	186087217	186087330
ENSE00001406979	186087443	186087645
ENSE00001407590	186087932	186088013
ENSE00001410657	186094276	186094373
ENSE00001410980	186090758	186090917
ENSE00001412270	186093486	186093669
ENSE00001429948	186095243	186095521
ENSE00001444756	186070612	186070757
ENSE00001890722	186189512	186190949
ENSE00003484168	185963768	185963895
ENSE00003495983	185984169	185984313
ENSE00003511803	185982262	185982389
ENSE00003515234	185977787	185977981
ENSE00003521847	185989488	185989647
ENSE00003549837	185980978	185981073
ENSE00003596468	185990275	185990443
ENSE00003614800	185965802	185965915
ENSE00003615061	186171337	186171450
ENSE00003660622	185970335	185970493
ENSE00003681926	185987432	185987544

Expression profiles

Bgee: expression breadth ubiquitous, 211 present calls, max score 95.40.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.9312 / max 486.7310, expressed in 938 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
7277	4.5293	804
7276	1.8491	585
7275	0.5528	340

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
descending thoracic aorta	UBERON:0002345	95.40	gold quality
thoracic aorta	UBERON:0001515	95.04	gold quality
ascending aorta	UBERON:0001496	94.99	gold quality
right coronary artery	UBERON:0001625	93.90	gold quality
visceral pleura	UBERON:0002401	93.90	gold quality
skin of hip	UBERON:0001554	90.71	gold quality
lower esophagus muscularis layer	UBERON:0035833	88.28	gold quality
lower esophagus	UBERON:0013473	88.20	gold quality
coronary artery	UBERON:0001621	87.36	gold quality
left coronary artery	UBERON:0001626	87.22	gold quality
layer of synovial tissue	UBERON:0007616	86.78	gold quality
synovial joint	UBERON:0002217	86.70	gold quality
cardiac muscle of right atrium	UBERON:0003379	86.59	silver quality
aorta	UBERON:0000947	86.47	gold quality
lung	UBERON:0002048	86.25	gold quality
right lung	UBERON:0002167	85.64	gold quality
calcaneal tendon	UBERON:0003701	85.63	gold quality
upper lobe of left lung	UBERON:0008952	85.38	gold quality
secondary oocyte	CL:0000655	85.25	gold quality
upper lobe of lung	UBERON:0008948	85.15	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	84.42	gold quality
parietal pleura	UBERON:0002400	83.51	gold quality
germinal epithelium of ovary	UBERON:0001304	82.71	gold quality
stromal cell of endometrium	CL:0002255	82.35	gold quality
mammalian vulva	UBERON:0000997	81.94	gold quality
mammary duct	UBERON:0001765	81.79	gold quality
epithelium of mammary gland	UBERON:0003244	81.58	gold quality
oocyte	CL:0000023	81.21	gold quality
thoracic mammary gland	UBERON:0005200	80.94	gold quality
artery	UBERON:0001637	80.83	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-75367	yes	41.75
E-ANND-3	yes	9.86
E-CURD-53	no	65.75

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTCF

miRNA regulators (miRDB)

88 targeting HMCN1, 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-5692A	100.00	74.40	6850
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4713-3P	100.00	65.92	505
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-5682	99.89	72.56	1005

Literature-anchored findings (GeneRIF, showing 19)

• We mapped the ARMD1 gene. Identification of the genes involved in AMD will lead to a better understanding of this disease at the molecular level. (PMID:14570714)
• None of our subjects (258 macular degeneration,AMD, cases, 72 non-AMD controls) had the Gln5345Arg variant in the HMCN1 gene. (PMID:16885922)
• We were not able to demonstrate an association between the Hemicentin-1, hOgg1, and E-selectin SNPs and age-related macular degeneration development in the currently available cases and controls. (PMID:17057786)
• The CFH gene and Hemicentin-1 genes do not appear to be involved in a statistically significant fraction of dry AMD (age-related macular degeneration) cases in the Japanese population. (PMID:17157600)
• Data shows that low-frequency variants encoding possible functional amino acid polymorphisms in the HMCN1 gene may not contribute substantially to disease, but HMCN1 mutations may still confer disease susceptibility in a small subset of patients. (PMID:17216616)
• hemicentin-1 gene appears to play a role in both age-related macular degeneration and renal pathophysiology (PMID:17591627)
• down-regulated in salivary gland epithelial cell from Sjogren’s syndrome patients following in vitro treatment with anti-Ro/SSA auto-antibodies; associated with increase in anoikis cell death (PMID:19190085)
• Dysregulation of fibulin expression by anti-Ro/SSA antibodies may contribute to disorganization of the extracellular environment and thus cause injury to the salivary gland architecture and functionality observed in Sjogren syndrome (PMID:19229767)
• Constructs show that EGF repeats 4 and 5 are required for hemicentin-dependent assembly and function of transgenic fibulin-1D in native locations. (PMID:22981695)
• this is the first association study based on a candidate gene approach to confirm that a HMCN1 polymorphism (rs2891230) is associated with postpartum depression diagnosis. heterozygosity (GA) for this SNP was associated with an increased risk of PPD. (PMID:24604465)
• HMCN1 mutation is associated with gastric and colorectal cancers. (PMID:24912920)
• Fibulin-6, a fibroblast-released extracellular matrix protein, may play an important role during myocardial remodelling by imparting an effect on cardiac fibroblasts migration in close and complementary interplay with TGF-beta1 signalling (PMID:24951538)
• The identified variants of HMCN1 are on conserved domains, particularly the two variants on calcium-binding epidermal growth factor domain. (PMID:25338956)
• A null-variant in HMCN1 (c.4162delC), has been identified in a Tunisian Jewish family with early-onset age-related macular degeneration. (PMID:25986072)
• Identify HMCN1 as a new molecule involved in the dynamic changes of podocyte foot processes in glomerular disease. (PMID:29488390)
• In the group that combined individuals affected by isolated cleft lip and palate, tooth agenesis, supernumerary teeth, molar incisor hypomineralization, or dental caries, we found an association with rs622260 but not with the rs10798049 marker. We determined that allele C of rs622260 was overrepresented in all individuals studied compared with a group of unrelated individuals who did not present any of these conditions. (PMID:29500156)
• the findings of the present study suggest that targeting the Cancerassociated fibroblasts genes, SRPX and HMCN1, can inhibit ovarian cancer migration and invasion. (PMID:31638245)
• HOXD9 aggravates the development of cervical cancer by transcriptionally activating HMCN1. (PMID:32414224)
• Comprehensive Analysis of HMCN1 Somatic Mutation in Clear Cell Renal Cell Carcinoma. (PMID:35886066)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	hmcn1	ENSDARG00000016936
danio_rerio	hmcn2	ENSDARG00000086060
mus_musculus	Hmcn1	ENSMUSG00000066842
rattus_norvegicus	Hmcn1	ENSRNOG00000028627
drosophila_melanogaster	bt	FBGN0005666
caenorhabditis_elegans		WBGENE00001000
caenorhabditis_elegans		WBGENE00006759

Paralogs (9): SPEG (ENSG00000072195), MYOT (ENSG00000120729), PALLD (ENSG00000129116), ALPK3 (ENSG00000136383), MYPN (ENSG00000138347), OBSCN (ENSG00000154358), IGFN1 (ENSG00000163395), CCDC141 (ENSG00000163492), SPEGNB (ENSG00000286095)

Protein

Protein identifiers

Hemicentin-1 — Q96RW7 (reviewed: Q96RW7)

Alternative names: Fibulin-6

All UniProt accessions (2): Q96RW7, Q5TCP6

UniProt curated annotations — full annotation on UniProt →

Function. Involved in transforming growth factor beta-mediated rearrangement of the podocyte cytoskeleton which includes reduction of F-actin fibers and broadening, flattening and elongation of podocytes. Plays a role in basement membrane organization. May promote cleavage furrow maturation during cytokinesis in preimplantation embryos. May play a role in the architecture of adhesive and flexible epithelial cell junctions. May play a role during myocardial remodeling by imparting an effect on cardiac fibroblast migration.

Subcellular location. Secreted. Extracellular space. Extracellular matrix. Basement membrane. Cytoplasm. Cell junction. Cleavage furrow.

Tissue specificity. Expressed in hair follicles and in the dermis (at protein level). Expressed in skin fibroblasts and retinal pigment epithelium (RPE) cells. Expressed in skin fibroblasts and retinal pigment epithelium (RPE) cells.

Disease relevance. Macular degeneration, age-related, 1 (ARMD1) [MIM:603075] A form of age-related macular degeneration, a multifactorial eye disease and the most common cause of irreversible vision loss in the developed world. In most patients, the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane. The disease is caused by variants affecting the gene represented in this entry.

Induction. Induced by high glucose levels and transforming growth factor beta (at protein level).

Isoforms (3)

UniProt ID	Names	Canonical?
Q96RW7-1	1	yes
Q96RW7-2	2
Q96RW7-3	3

RefSeq proteins (1): NP_114141* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000152	EGF-type_Asp/Asn_hydroxyl_site	PTM
IPR000742	EGF	Domain
IPR000884	TSP1_rpt	Repeat
IPR001881	EGF-like_Ca-bd_dom	Domain
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR006605	G2_nidogen/fibulin_G2F	Domain
IPR007110	Ig-like_dom	Domain
IPR009017	GFP	Homologous_superfamily
IPR009030	Growth_fac_rcpt_cys_sf	Homologous_superfamily
IPR013098	Ig_I-set	Domain
IPR013106	Ig_V-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR018097	EGF_Ca-bd_CS	Conserved_site
IPR026823	cEGF	Domain
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR036383	TSP1_rpt_sf	Homologous_superfamily
IPR036465	vWFA_dom_sf	Homologous_superfamily
IPR049883	NOTCH1_EGF-like	Domain
IPR050958	Cell_Adh-Cytoskel_Orgn	Family
IPR056475	GBD_Hemicentin/VWA7	Domain
IPR056861	HMCN1-like_VWA	Domain

Pfam: PF00090, PF07474, PF07645, PF07679, PF12662, PF13927, PF23560, PF25106

UniProt features (212 total): disulfide bond 76, domain 59, glycosylation site 34, sequence conflict 26, sequence variant 11, splice variant 4, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

No AlphaFold model available for Q96RW7 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

Functional residue map

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

Disulfide bonds (76): 911–960, 1002–1051, 1101–1150, 1192–1241, 1288–1338, 1382–1431, 1475–1525, 1569–1618, 1663–1712, 1756–1805, 1848–1898, 1942–1991, 2033–2083, 2125–2174, 2218–2269, 2314–2363, 2408–2457, 2501–2550, 2597–2646, 2696–2745 …

Glycosylation sites (34): 349, 390, 528, 550, 573, 620, 693, 809, 970, 1158, 1272, 1369, 1552, 1929, 2112, 2155, 2395, 2689, 2887, 2973 …

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 188 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, AAGCAAT_MIR137, GOBP_HETEROPHILIC_CELL_CELL_ADHESION, HNF3ALPHA_Q6, AREB6_03, GOZGIT_ESR1_TARGETS_DN, FOXO1_01, GOBP_CELL_CELL_ADHESION, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, FREAC3_01, GOMF_EXTRACELLULAR_MATRIX_STRUCTURAL_CONSTITUENT, GOBP_SENSORY_PERCEPTION_OF_LIGHT_STIMULUS, KINSEY_TARGETS_OF_EWSR1_FLII_FUSION_DN, HFH8_01, FOXJ2_01

GO Biological Process (7): homophilic cell-cell adhesion (GO:0007156), heterophilic cell-cell adhesion (GO:0007157), visual perception (GO:0007601), response to bacterium (GO:0009617), actin cytoskeleton organization (GO:0030036), cell division (GO:0051301), basement membrane organization (GO:0071711)

GO Molecular Function (4): extracellular matrix structural constituent (GO:0005201), calcium ion binding (GO:0005509), cell adhesion mediator activity (GO:0098631), protein binding (GO:0005515)

GO Cellular Component (12): basement membrane (GO:0005604), cytoplasm (GO:0005737), plasma membrane (GO:0005886), adherens junction (GO:0005912), muscle tendon junction (GO:0005927), cell cortex (GO:0005938), extracellular matrix (GO:0031012), cleavage furrow (GO:0032154), extracellular exosome (GO:0070062), extracellular region (GO:0005576), cell junction (GO:0030054), anchoring junction (GO:0070161)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cell-cell adhesion	2
extracellular matrix	2
cell periphery	2
sensory perception of light stimulus	1
response to other organism	1
cytoskeleton organization	1
actin filament-based process	1
cellular process	1
extracellular matrix organization	1
structural molecule activity	1
metal ion binding	1
cell adhesion	1
cell adhesion molecule binding	1
binding	1
intracellular anatomical structure	1
membrane	1
cell-cell junction	1
cell-substrate junction	1
cytoplasm	1
external encapsulating structure	1
cell division site	1
plasma membrane region	1
extracellular vesicle	1
cell junction	1

Protein interactions and networks

STRING

1342 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HMCN1	ARMS2	P0C7Q2	800
HMCN1	C2	P06681	679
HMCN1	FRAS1	Q86XX4	679
HMCN1	PLEKHA1	Q9HB21	666
HMCN1	RAX2	Q96IS3	632
HMCN1	ABCA4	P78363	623
HMCN1	CFH	P08603	615
HMCN1	CFHR3	Q02985	598
HMCN1	MUC16	Q8WXI7	582
HMCN1	CSMD3	Q7Z407	580
HMCN1	CFHR1	Q03591	576
HMCN1	SLC36A3	Q495N2	564
HMCN1	CFB	P00751	563
HMCN1	SYNE1	Q8NF91	544
HMCN1	CST3	P01034	525

IntAct

15 interactions, top by confidence:

A	B	Type	Score
HMCN1	ARMS2	psi-mi:“MI:0915”(physical association)	0.580
ARMS2	HMCN1	psi-mi:“MI:0915”(physical association)	0.580
HMCN1	B2M	psi-mi:“MI:0915”(physical association)	0.400
CDH5	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
CDH5	MYO1C	psi-mi:“MI:2364”(proximity)	0.270
fusA	HMCN1	psi-mi:“MI:0915”(physical association)	0.000
HMCN1		psi-mi:“MI:0915”(physical association)	0.000
	HMCN1	psi-mi:“MI:0915”(physical association)	0.000
murC	HMCN1	psi-mi:“MI:0915”(physical association)	0.000
hslU	HMCN1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (12): HMCN1 (Affinity Capture-MS), CLP1 (Co-fractionation), HMCN1 (Affinity Capture-MS), HMCN1 (Affinity Capture-MS), HMCN1 (Protein-RNA), HMCN1 (Proximity Label-MS), HMCN1 (Affinity Capture-MS), HMCN1 (Affinity Capture-MS), HMCN1 (Affinity Capture-MS), HMCN1 (Cross-Linking-MS (XL-MS)), HMCN1 (Affinity Capture-MS), HMCN1 (Co-fractionation)

ESM2 similar proteins: A0A140LHF2, A2AJ76, A6H8M9, A8T688, D3YXG0, E7FF10, O60500, P0C0L4, P0C0L5, P21709, P35590, P43121, P50895, P55144, P55146, P59996, P85171, Q00657, Q05695, Q06805, Q06806, Q0PMG2, Q13308, Q3UH53, Q53RD9, Q60750, Q62786, Q7Z5N4, Q8BKG3, Q8HW98, Q8IZJ3, Q8N0Z9, Q8NBP7, Q8NDA2, Q8NFP4, Q8TDY8, Q923P0, Q96MS0, Q96NU0, Q96RW7

Diamond homologs: A0A6I8RMG7, A2AJ76, B3EWY9, B5DFC9, O35568, O77469, O88322, P10493, P14543, P41413, P48960, P98095, Q04592, Q09165, Q14112, Q19267, Q2KIT5, Q2Q421, Q2Q426, Q4G063, Q4V7F2, Q4V7M2, Q5EA46, Q5RBP1, Q5XH36, Q60438, Q6UXH1, Q6UXI9, Q7SXF6, Q7ZXL5, Q86XX4, Q8BPB5, Q8K4G1, Q8R4U0, Q8R4Y4, Q91XD7, Q96HD1, Q96RW7, Q9CYA0, Q9JJS0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

3862 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	2283
Likely benign	1195
Benign	127

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
217863	NM_031935.3(HMCN1):c.4163del (p.Pro1388fs)	Pathogenic

SpliceAI

16108 predictions. Top by Δscore:

Variant	Effect	Δscore
1:185735046:AGGTA:A	donor_loss	1.0000
1:185735048:G:GA	donor_loss	1.0000
1:185846021:CACA:C	acceptor_loss	1.0000
1:185846022:A:AG	acceptor_gain	1.0000
1:185846023:C:G	acceptor_gain	1.0000
1:185846024:A:AG	acceptor_gain	1.0000
1:185846024:A:T	acceptor_loss	1.0000
1:185846025:G:GT	acceptor_gain	1.0000
1:185846025:GA:G	acceptor_gain	1.0000
1:185846025:GAA:G	acceptor_gain	1.0000
1:185846025:GAAA:G	acceptor_gain	1.0000
1:185846025:GAAAT:G	acceptor_gain	1.0000
1:185846096:GGTG:G	donor_loss	1.0000
1:185846097:G:GG	donor_gain	1.0000
1:185846098:T:G	donor_loss	1.0000
1:185864465:AACAG:A	acceptor_gain	1.0000
1:185864466:ACAG:A	acceptor_gain	1.0000
1:185864467:CAG:C	acceptor_loss	1.0000
1:185864468:AG:A	acceptor_gain	1.0000
1:185864468:AGG:A	acceptor_gain	1.0000
1:185864468:AGGGT:A	acceptor_gain	1.0000
1:185864469:G:A	acceptor_gain	1.0000
1:185864469:GGG:G	acceptor_gain	1.0000
1:185864469:GGGT:G	acceptor_gain	1.0000
1:185864469:GGGTG:G	acceptor_gain	1.0000
1:185864628:AG:A	donor_loss	1.0000
1:185864629:GTGA:G	donor_gain	1.0000
1:185864631:GA:G	donor_gain	1.0000
1:185864632:A:AC	donor_loss	1.0000
1:185864633:G:GG	donor_gain	1.0000

AlphaMissense

36816 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:185734919:A:T	D47V	1.000
1:185846077:T:C	L107P	1.000
1:185864482:T:C	C118R	1.000
1:185864561:A:T	D144V	1.000
1:185865751:T:A	V170D	1.000
1:185734910:T:C	F44S	0.999
1:185734918:G:C	D47H	0.999
1:185734919:A:C	D47A	0.999
1:185734919:A:G	D47G	0.999
1:185734920:T:A	D47E	0.999
1:185734920:T:G	D47E	0.999
1:185734927:G:C	G50R	0.999
1:185734927:G:T	G50C	0.999
1:185734928:G:A	G50D	0.999
1:185734946:T:C	L56S	0.999
1:185734967:C:A	A63D	0.999
1:185735035:T:C	F86L	0.999
1:185735037:C:A	F86L	0.999
1:185735037:C:G	F86L	0.999
1:185846065:T:C	F103S	0.999
1:185846077:T:A	L107H	0.999
1:185846086:T:C	L110P	0.999
1:185864482:T:A	C118S	0.999
1:185864483:G:A	C118Y	0.999
1:185864483:G:C	C118S	0.999
1:185864484:C:G	C118W	0.999
1:185864494:A:C	S122R	0.999
1:185864496:T:A	S122R	0.999
1:185864496:T:G	S122R	0.999
1:185864507:T:A	I126K	0.999

dbSNP variants (sampled 300 via entrez): RS1000010773 (1:186026475 G>A,C,T), RS1000026423 (1:185855099 G>C), RS1000037344 (1:186109555 A>G), RS1000047272 (1:186116557 TAAAC>T), RS1000053729 (1:185933493 T>C), RS1000058419 (1:185975620 C>T), RS1000070013 (1:185844943 A>G), RS1000073836 (1:185768370 G>T), RS1000078409 (1:185992262 A>G,T), RS1000082311 (1:185803253 G>A,T), RS1000101993 (1:186172634 A>G,T), RS1000113771 (1:186044544 T>C,G), RS1000119542 (1:186107125 G>A,T), RS1000120760 (1:186021630 A>G), RS1000121807 (1:185775909 A>G,T)

Disease associations

OMIM: gene MIM:608548 | disease phenotypes: MIM:603075

GenCC curated gene-disease

Disease	Classification	Inheritance
age related macular degeneration 1	Limited	Autosomal dominant

Mondo (2): age related macular degeneration 1 (MONDO:0011285), prostate cancer (MONDO:0008315)

Orphanet (1): Familial prostate cancer (Orphanet:1331)

HPO phenotypes

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

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000529	Progressive visual loss
HP:0000608	Macular degeneration
HP:0003584	Late onset
HP:0011506	Choroidal neovascularization
HP:0012643	Foveal hypopigmentation
HP:0025574	Macular hemorrhage
HP:0030499	Macular drusen
HP:0031609	Macular geographic atrophy

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST001920_9	QRS duration	9.000000e-06
GCST003815_70	Late-onset Alzheimer’s disease	1.000000e-06
GCST008156_57	Hip circumference adjusted for BMI	4.000000e-06
GCST008162_48	Hip circumference	5.000000e-06
GCST90000025_838	Appendicular lean mass	4.000000e-10

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:1001870	late-onset Alzheimers disease
EFO:0008039	BMI-adjusted hip circumference
EFO:0004980	appendicular lean mass

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750
C566411	Macular Degeneration, Age-Related, 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression	6
Benzo(a)pyrene	affects expression, affects methylation, decreases expression, increases methylation	4
trichostatin A	affects cotreatment, increases expression	3
bisphenol A	affects methylation, decreases expression	2
mono-(2-ethylhexyl)phthalate	decreases expression	2
sodium arsenite	decreases expression, increases expression	2
Estradiol	affects cotreatment, increases expression	2
Nickel	decreases expression	2
Tobacco Smoke Pollution	decreases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
aristolochic acid I	decreases expression	1
daidzein	affects cotreatment, increases expression	1
methylmercuric chloride	decreases expression	1
lasiocarpine	decreases expression	1
methyleugenol	decreases expression	1
daidzin	affects cotreatment, increases expression	1
ochratoxin A	increases expression	1
benzo(e)pyrene	increases methylation	1
genistin	affects cotreatment, increases expression	1
glycitein	affects cotreatment, increases expression	1
CGP 52608	affects binding, increases reaction	1
glycitin	increases expression, affects cotreatment	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
incobotulinumtoxinA	increases expression	1
(+)-JQ1 compound	decreases expression	1
Dasatinib	increases expression	1
Zoledronic Acid	decreases expression	1
Acetaminophen	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT07403825	PHASE4	RECRUITING	Efficacy of Faricimab in Patients With Subretinal Hyper-reflective Material
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer