CPAMD8

Summary

CPAMD8 (C3 and PZP like alpha-2-macroglobulin domain containing 8, HGNC:23228) is a protein-coding gene on chromosome 19p13.11, encoding C3 and PZP-like alpha-2-macroglobulin domain-containing protein 8 (Q8IZJ3). It is a selective cancer dependency (DepMap: 31.0% of cell lines).

This gene encodes a member of the protease inhibitor I39 (alpha-2-macroglobulin) family of proteins. These proteins are important in innate and acquired immunity. The encoded protein is membrane-associated and proteolytically processed to generate two chains. Mutations in this gene cause a form of anterior segment dysgenesis, a developmental disorder of the eye.

Source: NCBI Gene 27151 — RefSeq curated summary.

At a glance

• Gene–disease (curated): anterior segment dysgenesis 8 (Definitive, ClinGen)
• GWAS associations: 5
• Clinical variants (ClinVar): 726 total — 11 pathogenic, 15 likely-pathogenic
• Phenotypes (HPO): 14
• Cancer dependency (DepMap): dependent in 31.0% of screened cell lines
• MANE Select transcript: NM_015692

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23228
Approved symbol	CPAMD8
Name	C3 and PZP like alpha-2-macroglobulin domain containing 8
Location	19p13.11
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1283, VIP, K-CAP
Ensembl gene	ENSG00000160111
Ensembl biotype	protein_coding
OMIM	608841
Entrez	27151

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 8 retained_intron, 6 protein_coding, 6 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000291440, ENST00000443236, ENST00000593420, ENST00000593739, ENST00000594249, ENST00000595323, ENST00000596224, ENST00000596572, ENST00000597335, ENST00000597709, ENST00000598547, ENST00000598792, ENST00000599287, ENST00000600235, ENST00000601637, ENST00000601782, ENST00000602132, ENST00000602159, ENST00000651564, ENST00000682780, ENST00000942844

RefSeq mRNA: 1 — MANE Select: NM_015692 NM_015692

CCDS: CCDS42519

Canonical transcript exons

ENST00000443236 — 42 exons

Exon	Start	End
ENSE00001049832	17004273	17004386
ENSE00001049835	17011464	17011516
ENSE00001049836	17002266	17002350
ENSE00001049837	17020331	17020353
ENSE00001049839	16976002	16976151
ENSE00001049841	16977368	16977540
ENSE00001049844	16980497	16980686
ENSE00001049846	17008505	17008559
ENSE00001049852	16997111	16997338
ENSE00001049856	16993416	16993586
ENSE00001049861	17022030	17022181
ENSE00001049866	17000414	17000522
ENSE00001049868	16989643	16989771
ENSE00001049874	17011592	17011757
ENSE00001627168	16938395	16938446
ENSE00001628384	16892951	16893339
ENSE00001640220	16928942	16929240
ENSE00001670938	16914424	16914498
ENSE00001671423	16928009	16928234
ENSE00001675617	16945549	16945679
ENSE00001679971	16899475	16899549
ENSE00001683140	16951969	16952200
ENSE00001708257	16947074	16947227
ENSE00001719634	17009303	17009320
ENSE00001731926	16902649	16902863
ENSE00001733458	16921905	16921986
ENSE00001744031	16906952	16907117
ENSE00001748335	16897889	16897994
ENSE00001754258	16901210	16901297
ENSE00001756382	16914657	16914813
ENSE00001758732	16925196	16925372
ENSE00001784840	16903561	16903623
ENSE00001797460	16904226	16904362
ENSE00001801042	16903702	16903857
ENSE00001801196	16904466	16904552
ENSE00003461477	16970891	16971033
ENSE00003489366	16897691	16897801
ENSE00003507743	16957853	16957915
ENSE00003571704	16975097	16975258
ENSE00003616619	16896456	16896665
ENSE00003629603	16896176	16896326
ENSE00003901282	17026551	17026810

Expression profiles

Bgee: expression breadth ubiquitous, 227 present calls, max score 94.22.

FANTOM5 (CAGE): breadth broad, TPM avg 0.7554 / max 24.3920, expressed in 410 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
179829	0.6396	337
208721	0.0988	53
179830	0.0171	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	94.22	gold quality
pancreatic ductal cell	CL:0002079	90.69	gold quality
right lung	UBERON:0002167	90.06	gold quality
metanephros cortex	UBERON:0010533	89.56	gold quality
ventricular zone	UBERON:0003053	88.98	gold quality
heart left ventricle	UBERON:0002084	88.25	gold quality
prostate gland	UBERON:0002367	88.15	gold quality
cardiac ventricle	UBERON:0002082	87.80	gold quality
tibia	UBERON:0000979	86.87	gold quality
upper lobe of left lung	UBERON:0008952	86.58	gold quality
lateral globus pallidus	UBERON:0002476	86.21	gold quality
endocervix	UBERON:0000458	85.58	gold quality
kidney epithelium	UBERON:0004819	85.58	silver quality
upper lobe of lung	UBERON:0008948	85.46	gold quality
left lobe of thyroid gland	UBERON:0001120	84.78	gold quality
metanephros	UBERON:0000081	84.57	gold quality
thyroid gland	UBERON:0002046	84.10	gold quality
lung	UBERON:0002048	82.89	gold quality
adult mammalian kidney	UBERON:0000082	82.88	gold quality
corpus epididymis	UBERON:0004359	82.82	gold quality
heart	UBERON:0000948	82.43	gold quality
parotid gland	UBERON:0001831	82.36	gold quality
ganglionic eminence	UBERON:0004023	82.27	gold quality
embryo	UBERON:0000922	82.26	gold quality
layer of synovial tissue	UBERON:0007616	82.26	gold quality
right lobe of thyroid gland	UBERON:0001119	82.18	gold quality
substantia nigra	UBERON:0002038	82.07	gold quality
seminal vesicle	UBERON:0000998	81.73	gold quality
left ventricle myocardium	UBERON:0006566	81.60	silver quality
spinal cord	UBERON:0002240	81.53	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-11121	yes	930.78
E-ANND-3	yes	8.59
E-GEOD-99795	no	10.24

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

15 targeting CPAMD8, 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-4455	100.00	65.48	1587
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-6772-5P	99.94	67.01	577
HSA-MIR-609	99.82	64.26	505
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-4269	99.55	69.89	1373
HSA-MIR-217-5P	99.49	69.93	1419
HSA-MIR-6807-3P	99.15	69.23	1275
HSA-MIR-4254	99.11	65.15	1315
HSA-MIR-6776-5P	98.54	67.43	1304
HSA-MIR-5589-5P	98.34	64.82	1148
HSA-MIR-630	97.50	66.38	921
HSA-MIR-1245A	96.33	66.25	498
HSA-MIR-8079	96.33	66.11	484

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 31.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 5)

• a novel member of the complement 3/alpha(2)-macroglobulin (C3/alpha(2)M) family named CPAMD8 has been identified and characterized. (PMID:15177561)
• study delineates a unique form of recessive anterior segment dysgeneses (ASD) and defines a role for CPAMD8, a protein of unknown function, in anterior segment development, implying another pathway for the pathogenicity of ASD (PMID:27839872)
• Biallelic CPAMD8 Variants Are a Frequent Cause of Childhood and Juvenile Open-Angle Glaucoma. (PMID:32085876)
• CPAMD8 loss-of-function underlies non-dominant congenital glaucoma with variable anterior segment dysgenesis and abnormal extracellular matrix. (PMID:32274568)
• Biallelic variants in CPAMD8 are associated with primary open-angle glaucoma and primary angle-closure glaucoma. (PMID:34154991)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	cpamd8	ENSDARG00000056530
mus_musculus	Mug2	ENSMUSG00000030131
mus_musculus	Mug1	ENSMUSG00000059908
mus_musculus	Gm7298	ENSMUSG00000108022
rattus_norvegicus	Cpamd8	ENSRNOG00000065350
rattus_norvegicus	Mug1l1	ENSRNOG00000070375
rattus_norvegicus		ENSRNOG00000075610
rattus_norvegicus		ENSRNOG00000091232

Paralogs (8): C5 (ENSG00000106804), C3 (ENSG00000125730), PZP (ENSG00000126838), CD109 (ENSG00000156535), A2ML1 (ENSG00000166535), A2M (ENSG00000175899), C4B (ENSG00000224389), C4A (ENSG00000244731)

Protein

Protein identifiers

C3 and PZP-like alpha-2-macroglobulin domain-containing protein 8 — Q8IZJ3 (reviewed: Q8IZJ3)

All UniProt accessions (6): Q8IZJ3, A0A494C0S9, A0A804HKX4, F8W7D1, M0QXH3, M0R3G7

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Interacts with heparin.

Subcellular location. Secreted. Cell membrane.

Tissue specificity. Highly expressed in the kidney, brain and testis and to a lower extent in heart, liver and small intestine. Expressed in the lens, cornea and retina. Strongly expressed in the distal tips of the retinal neuroepithelium that form the iris and ciliary body.

Post-translational modifications. Proteolytically cleaved into 2 chains of about 70 and 130 kDa. The fragments are not connected by disulfide bonds.

Disease relevance. Anterior segment dysgenesis 8 (ASGD8) [MIM:617319] A form of anterior segment dysgenesis, a group of defects affecting anterior structures of the eye including cornea, iris, lens, trabecular meshwork, and Schlemm canal. Anterior segment dysgeneses result from abnormal migration or differentiation of the neural crest derived mesenchymal cells that give rise to components of the anterior chamber during eye development. Different anterior segment anomalies may exist alone or in combination, including iris hypoplasia, enlarged or reduced corneal diameter, corneal vascularization and opacity, posterior embryotoxon, corectopia, polycoria, abnormal iridocorneal angle, ectopia lentis, and anterior synechiae between the iris and posterior corneal surface. Clinical conditions falling within the phenotypic spectrum of anterior segment dysgeneses include aniridia, Axenfeld anomaly, Reiger anomaly/syndrome, Peters anomaly, and iridogoniodysgenesis. ASGD8 patients predominantly manifest iris and lens abnormalities, in the absence of retinal abnormalities or extra-ocular features. ASGD8 transmission pattern is consistent with autosomal recessive inheritance. The disease is caused by variants affecting the gene represented in this entry.

Induction. Up-regulated by IL1B/interleukin-1 beta and IL6/interleukin-6.

Similarity. Belongs to the protease inhibitor I39 (alpha-2-macroglobulin) family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8IZJ3-1	1	yes
Q8IZJ3-2	2

RefSeq proteins (1): NP_056507* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001599	Macroglobln_a2	Domain
IPR002350	Kazal_dom	Domain
IPR002890	MG2	Domain
IPR008930	Terpenoid_cyclase/PrenylTrfase	Homologous_superfamily
IPR009048	A-macroglobulin_rcpt-bd	Domain
IPR011625	A2M_N_BRD	Domain
IPR011626	Alpha-macroglobulin_TED	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR014756	Ig_E-set	Homologous_superfamily
IPR019742	MacrogloblnA2_CS	Conserved_site
IPR022041	Methyltransf_FA	Domain
IPR036058	Kazal_dom_sf	Homologous_superfamily
IPR036595	A-macroglobulin_rcpt-bd_sf	Homologous_superfamily
IPR040839	MG4	Domain
IPR041555	MG3	Domain
IPR041813	A2M_TED	Domain
IPR047565	Alpha-macroglob_thiol-ester_cl	Conserved_site
IPR050473	A2M/Complement_sys	Family

Pfam: PF00207, PF01835, PF07648, PF07677, PF07678, PF07703, PF12248, PF17789, PF17791

UniProt features (29 total): sequence variant 10, glycosylation site 5, disulfide bond 3, splice variant 2, region of interest 2, compositionally biased region 2, signal peptide 1, chain 1, domain 1, sequence conflict 1, site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IZJ3-F1	72.99	0.18

Functional residue map

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

Catalytic / active sites (1): 671–672 (cleavage; by furin-like protease)

Disulfide bonds (3): 1712–1742, 1716–1735, 1724–1755

Glycosylation sites (5): 267, 757, 1439, 117, 190

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 270 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_DN, ATF_B, MODULE_92, REACTOME_GLUCAGON_TYPE_LIGAND_RECEPTORS, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, NKX25_02, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_HORMONE_TRANSPORT, STAT3_01, AAAYRNCTG_UNKNOWN, GOBP_CELL_CELL_SIGNALING, GOBP_ORGANIC_HYDROXY_COMPOUND_TRANSPORT

GO Biological Process (1): eye development (GO:0001654)

GO Molecular Function (4): serine-type endopeptidase inhibitor activity (GO:0004867), endopeptidase inhibitor activity (GO:0004866), protein binding (GO:0005515), peptidase inhibitor activity (GO:0030414)

GO Cellular Component (4): obsolete extracellular space (GO:0005615), plasma membrane (GO:0005886), extracellular region (GO:0005576), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
sensory organ development	1
visual system development	1
serine-type endopeptidase activity	1
endopeptidase inhibitor activity	1
endopeptidase activity	1
peptidase inhibitor activity	1
endopeptidase regulator activity	1
binding	1
enzyme inhibitor activity	1
peptidase activity	1
peptidase regulator activity	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

680 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CPAMD8	FURIN	P09958	548
CPAMD8	TRIM58	Q8NG06	503
CPAMD8	GAA	P10253	448
CPAMD8	ADAMTSL4	Q6UY14	439
CPAMD8	GPATCH3	Q96I76	438
CPAMD8	IQCC	Q4KMZ1	423
CPAMD8	PROSER3	Q2NL68	402
CPAMD8	P3H2	Q8IVL5	401
CPAMD8	MYOC	Q99972	398
CPAMD8	LTBP2	Q14767	396
CPAMD8	PRSS48	Q7RTY5	371
CPAMD8	LTBP3	Q9NS15	366
CPAMD8	OR2I1	Q8NGU4	355
CPAMD8	SH2D4B	Q5SQS7	347
CPAMD8	F2RL3	Q96RI0	344

IntAct

4 interactions, top by confidence:

A	B	Type	Score
CPAMD8	H2AC14	psi-mi:“MI:0915”(physical association)	0.400
CPAMD8	H2BC20P	psi-mi:“MI:0915”(physical association)	0.400
P		psi-mi:“MI:0914”(association)	0.350

BioGRID (8): CPAMD8 (Affinity Capture-RNA), CPAMD8 (Proximity Label-MS), HIST1H2AJ (Proximity Label-MS), CPAMD8 (Protein-peptide), SCTR (Protein-peptide), CPAMD8 (Protein-peptide), CPAMD8 (Positive Genetic), CPAMD8 (Affinity Capture-RNA)

ESM2 similar proteins: A0AAQ4VMX2, A0M8R7, A1X150, I2C090, O02668, P01029, P01030, P01031, P06238, P06684, P08581, P08649, P08650, P0C0L4, P0C0L5, P14046, P16056, P19069, P19823, P28665, P28666, P79263, P97523, P98093, P98094, Q00685, Q03626, Q07DY1, Q07DZ1, Q07E48, Q09YN5, Q108U6, Q14624, Q2IBA6, Q2IBC0, Q2IBD8, Q2IBF2, Q2IBG7, Q2QL89, Q2QLA9

Diamond homologs: A2ASQ1, D0NJ41, O00468, O96790, P00998, P01001, P05569, P05570, P05571, P05585, P05589, P05592, P05594, P05595, P05596, P05599, P05601, P09656, P0DKM7, P0DKM8, P0DKM9, P0DKT1, P0DKT2, P0DKT3, P0DKT4, P0DKT5, P10184, P16895, P19883, P25304, P31696, P52243, P52244, P52245, P52246, P52256, P52261, P58062, P67889, P67890

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	11
Likely pathogenic	15
Uncertain significance	385
Likely benign	115
Benign	161

Top pathogenic / likely-pathogenic (26)

Variant ID	HGVS	Classification
1906210	NM_015692.5(CPAMD8):c.114_117del (p.Ser39fs)	Pathogenic
1917220	NM_015692.5(CPAMD8):c.1881del (p.Arg627fs)	Pathogenic
2069858	NM_015692.5(CPAMD8):c.4024C>T (p.Arg1342Ter)	Pathogenic
2079185	NM_015692.5(CPAMD8):c.2002C>T (p.Arg668Ter)	Pathogenic
2086333	NM_015692.5(CPAMD8):c.1689C>A (p.Tyr563Ter)	Pathogenic
2628067	NM_015692.5(CPAMD8):c.3798_3861+1759del	Pathogenic
375309	NM_015692.5(CPAMD8):c.4210T>C (p.Ser1404Pro)	Pathogenic
375310	NM_015692.5(CPAMD8):c.2211dup (p.Arg738fs)	Pathogenic
375311	NM_015692.5(CPAMD8):c.4408-1G>A	Pathogenic
4702495	NM_015692.5(CPAMD8):c.2270del (p.Asn757fs)	Pathogenic
4738944	NM_015692.5(CPAMD8):c.4157C>A (p.Thr1386Asn)	Pathogenic
1333413	NM_015692.5(CPAMD8):c.2070+1G>C	Likely pathogenic
1710323	NM_015692.5(CPAMD8):c.1691dup (p.Arg565fs)	Likely pathogenic
2442072	NM_015692.5(CPAMD8):c.-55G>A	Likely pathogenic
2632198	NM_015692.5(CPAMD8):c.4407+2T>G	Likely pathogenic
2634581	NM_015692.5(CPAMD8):c.3724del (p.Gln1242fs)	Likely pathogenic
3235244	NM_015692.5(CPAMD8):c.4825C>T (p.Arg1609Ter)	Likely pathogenic
3235245	NM_015692.5(CPAMD8):c.534G>A (p.Trp178Ter)	Likely pathogenic
3250462	NM_015692.5(CPAMD8):c.2932C>T (p.Arg978Ter)	Likely pathogenic
3362554	NM_015692.5(CPAMD8):c.4396del (p.Gln1466fs)	Likely pathogenic
3382024	NM_015692.5(CPAMD8):c.3349C>T (p.Arg1117Ter)	Likely pathogenic
3911858	NM_015692.5(CPAMD8):c.404A>T (p.Asp135Val)	Likely pathogenic
4081285	NM_015692.5(CPAMD8):c.2070_2071insTTAA (p.Glu691fs)	Likely pathogenic
4292380	NM_015692.5(CPAMD8):c.3145-1G>T	Likely pathogenic
4849467	NM_015692.5(CPAMD8):c.2141del (p.Asp714fs)	Likely pathogenic
932293	NM_015692.5(CPAMD8):c.3008G>T (p.Gly1003Val)	Likely pathogenic

SpliceAI

6443 predictions. Top by Δscore:

Variant	Effect	Δscore
19:16899547:CAG:C	acceptor_gain	1.0000
19:16899550:C:CC	acceptor_gain	1.0000
19:16902646:TA:T	donor_loss	1.0000
19:16902648:C:CT	donor_loss	1.0000
19:16902859:TCAAT:T	acceptor_gain	1.0000
19:16902860:CAATC:C	acceptor_gain	1.0000
19:16902861:AAT:A	acceptor_gain	1.0000
19:16902862:AT:A	acceptor_gain	1.0000
19:16902864:C:CC	acceptor_gain	1.0000
19:16902871:G:GC	acceptor_gain	1.0000
19:16903697:CGCA:C	donor_loss	1.0000
19:16903699:CACC:C	donor_loss	1.0000
19:16903700:A:AC	donor_gain	1.0000
19:16903701:C:CT	donor_gain	1.0000
19:16903701:CCG:C	donor_gain	1.0000
19:16903853:GTGTC:G	acceptor_gain	1.0000
19:16903854:TGTC:T	acceptor_gain	1.0000
19:16903855:GTC:G	acceptor_gain	1.0000
19:16903856:TC:T	acceptor_gain	1.0000
19:16903857:CC:C	acceptor_gain	1.0000
19:16903857:CCT:C	acceptor_loss	1.0000
19:16903858:C:CC	acceptor_gain	1.0000
19:16903864:A:AC	acceptor_gain	1.0000
19:16903864:A:C	acceptor_gain	1.0000
19:16904276:T:TA	donor_gain	1.0000
19:16904360:CCA:C	acceptor_gain	1.0000
19:16904361:CA:C	acceptor_gain	1.0000
19:16904361:CAC:C	acceptor_gain	1.0000
19:16904363:C:CC	acceptor_gain	1.0000
19:16906947:CCTA:C	donor_loss	1.0000

AlphaMissense

12240 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:16904238:G:C	F1413L	0.997
19:16904238:G:T	F1413L	0.997
19:16904240:A:G	F1413L	0.997
19:16921934:A:C	F1200L	0.997
19:16921934:A:T	F1200L	0.997
19:16921936:A:G	F1200L	0.997
19:16903857:C:G	D1418H	0.996
19:16921977:C:G	R1186P	0.996
19:17004336:A:G	W204R	0.996
19:17004336:A:T	W204R	0.996
19:16902817:A:G	F1506S	0.995
19:16925196:C:G	G1183R	0.995
19:16925299:G:C	N1148K	0.995
19:16925299:G:T	N1148K	0.995
19:16997135:C:A	K357N	0.995
19:16997135:C:G	K357N	0.995
19:16901265:A:T	V1573D	0.994
19:16902816:G:C	F1506L	0.994
19:16902816:G:T	F1506L	0.994
19:16902817:A:C	F1506C	0.994
19:16902818:A:G	F1506L	0.994
19:16903856:T:A	D1418V	0.994
19:16952145:A:G	W778R	0.994
19:16952145:A:T	W778R	0.994
19:16976074:G:C	S612R	0.994
19:16976074:G:T	S612R	0.994
19:16976076:T:G	S612R	0.994
19:16993540:A:T	V381D	0.994
19:17011610:A:C	Y139D	0.994
19:16925258:A:G	L1162P	0.993

dbSNP variants (sampled 300 via entrez): RS1000003537 (19:16914303 C>T), RS1000020631 (19:16915109 C>T), RS1000031114 (19:16988365 T>C), RS1000058277 (19:16950281 G>A,C), RS1000100002 (19:16919449 T>C), RS1000114023 (19:16956607 A>G), RS1000137211 (19:16966771 A>T), RS1000172484 (19:16919222 G>T), RS1000252835 (19:16924770 G>A), RS1000258625 (19:16993805 G>A), RS1000273706 (19:16962084 A>C), RS1000286590 (19:16956729 G>A), RS1000310748 (19:16945126 C>T), RS1000357995 (19:16993561 C>G,T), RS1000384359 (19:17017627 C>T)

Disease associations

OMIM: gene MIM:608841 | disease phenotypes: MIM:617319, MIM:231300, MIM:107250

GenCC curated gene-disease

Disease	Classification	Inheritance
anterior segment dysgenesis 8	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
anterior segment dysgenesis 8	Definitive	AR

Mondo (4): anterior segment dysgenesis 8 (MONDO:0015017), breast ductal adenocarcinoma (MONDO:0005590), glaucoma 3A (MONDO:0009277), anterior segment dysgenesis (MONDO:0019503)

Orphanet (4): Autosomal recessive anterior segment dysgenesis (Orphanet:519388), Congenital glaucoma (Orphanet:98976), Juvenile glaucoma (Orphanet:98977), Anterior segment developmental anomaly (Orphanet:88632)

HPO phenotypes

14 total (14 of 14 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000518	Cataract
HP:0001083	Ectopia lentis
HP:0001093	Optic nerve dysplasia
HP:0007676	Hypoplasia of the iris
HP:0007957	Corneal opacity
HP:0009917	Persistent pupillary membrane
HP:0009918	Ectopia pupillae
HP:0011463	Childhood onset
HP:0012040	Corneal stromal edema
HP:0012376	Microphakia
HP:0012805	Iris transillumination defect
HP:0025358	Uveal ectropion
HP:0100693	Iridodonesis

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST000265_1	Brain lesion load	7.000000e-06
GCST001438_3	Crohn’s disease	7.000000e-09
GCST008163_15	Height	4.000000e-06
GCST009959_5	Retinal detachment or retinal break	1.000000e-06
GCST90014268_40	Cataracts	5.000000e-13

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010698	retinal break

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases mutagenesis, affects methylation, increases methylation	3
sodium arsenite	decreases expression, increases methylation	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	decreases expression, decreases methylation	2
afuresertib	increases expression	1
bufotalin	decreases expression	1
methylmercuric chloride	decreases expression	1
propionaldehyde	decreases expression	1
arsenite	increases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	increases expression	1
benzo(e)pyrene	affects methylation	1
aflatoxin B2	increases methylation	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Diethylhexyl Phthalate	decreases expression	1
Methapyrilene	affects methylation	1
Oxygen	increases expression	1
Valproic Acid	affects expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	increases methylation	1
Acrylamide	decreases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT00461344	PHASE2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	PHASE2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT00637364	PHASE1/PHASE2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	PHASE1/PHASE2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	EARLY_PHASE1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	EARLY_PHASE1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT01208974	Not specified	ACTIVE_NOT_RECRUITING	Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
NCT01875198	Not specified	TERMINATED	Oncologic Impact of Splenectomy-omitting Radical Pancreatectomy in Well-selected Left-sided Pancreatic Cancer
NCT03543397	Not specified	UNKNOWN	MRI in Ductal Carcinoma in Situ (DCIS)
NCT03834532	Not specified	COMPLETED	Living Well After Breast Surgery
NCT05641103	Not specified	COMPLETED	PREDIGA 2: Spanish Acronym of Educational and Diagnostic Project for Gaucher and ASMD