Atrioventricular septal defect, susceptibility to, 2

Summary

Atrioventricular septal defect, susceptibility to, 2 (MONDO:0011650) is a disease with 3 cohort genes.

At a glance

• Cohort genes: 3
• ClinVar variants: 114

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	atrioventricular septal defect, susceptibility to, 2
Mondo ID	MONDO:0011650
MeSH	C565249
OMIM	606217
UMLS	C1853508
MedGen	381193
Is cancer (heuristic)	no

Also known as: atrioventricular septal defect caused by mutation in CRELD1 · atrioventricular septal defect, susceptibility to, 2 · atrioventricular septal defect, susceptibility to, type 2 · AVSD2 · CRELD1 atrioventricular septal defect

Data availability: 114 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease susceptibility › inherited disease susceptibility › atrioventricular septal defect, susceptibility to, 2

Related subtypes (283): microvascular complications of diabetes, susceptibility, Mycobacterium tuberculosis, susceptibility, bacteremia, susceptibility, pregnancy loss, recurrent, susceptibility, autoimmune thyroid disease, susceptibility to, susceptibility to HIV infection, appendicitis, proneness to, atherosclerosis susceptibility, multiple sclerosis, susceptibility to, dyslexia, susceptibility to, 1, endometriosis, susceptibility to, 1, osteoarthritis susceptibility 2, essential hypertension, genetic, osteoarthritis susceptibility 1, otitis media, susceptibility to, pelvic organ prolapse, susceptibility to, pulmonary edema of mountaineers, susceptibility to, sarcoidosis, susceptibility to, 1, strabismus, susceptibility to, thyrotoxic periodic paralysis, susceptibility to, 1, predisposition to invasive fungal disease due to CARD9 deficiency, celiac disease, susceptibility to, 1, hemolytic uremic syndrome, atypical, susceptibility to, 1, hypervitaminosis a, susceptibility to, kuru, susceptibility to, leprosy, susceptibility to, 3, nonarteritic anterior ischemic optic neuropathy, susceptibility to, diabetes mellitus, insulin-dependent, X-linked, susceptibility to, coronary heart disease, susceptibility to, 3, dyslexia, susceptibility to, 9, systemic lupus erythematosus, susceptibility to, 15, Leber optic atrophy, susceptibility to, dyslexia, susceptibility to, 2, Helicobacter pylori infection, susceptibility to, epilepsy, idiopathic generalized, susceptibility to, 1, inherited susceptibility to asthma, renal dysplasia, cystic, susceptibility to, systemic lupus erythematosus, susceptibility to, 1, leishmaniasis, tegumentary, susceptibility to, xanthomatosis, susceptibility to, hyperlipidemia, combined, 1, urinary tract infections, recurrent, susceptibility to, hypertension, essential, susceptibility to, 1, hepatic fibrosis, severe, susceptibility to, due to Schistosoma mansoni infection, dyslexia, susceptibility to, 3, Ascaris lumbricoides infection, susceptibility to, hypertension, essential, susceptibility to, 2, epilepsy, idiopathic generalized, susceptibility to, 7, systemic lupus erythematosus, susceptibility to, 2, systemic lupus erythematosus, susceptibility to, 3, nephrolithiasis, uric acid, susceptibility to, vitiligo-associated multiple autoimmune disease susceptibility 1, polysubstance abuse, susceptibility to, dyslexia, susceptibility to, 6, glaucoma, normal tension, susceptibility to, anorexia nervosa, susceptibility to, 1, stroke, susceptibility to, 1, dyslexia, susceptibility to, 5, epilepsy, idiopathic generalized, susceptibility to, 2, familial meningioma, celiac disease, susceptibility to, 5, systemic lupus erythematosus with hemolytic anemia, susceptibility to, 1, hypertension, essential, susceptibility to, 3, coronary heart disease, susceptibility to, 1, bulimia nervosa, susceptibility to, 1, leprosy, susceptibility to, 2, epilepsy, idiopathic generalized, susceptibility to, 9, Parkinson disease 11, autosomal dominant, susceptibility to, focal segmental glomerulosclerosis 3, susceptibility to, autoimmune disease, susceptibility to, 1, osteoarthritis susceptibility 3, systemic lupus erythematosus with nephritis, susceptibility to, 1, systemic lupus erythematosus with nephritis, susceptibility to, 2, systemic lupus erythematosus with nephritis, susceptibility to, 3, coronary heart disease, susceptibility to, 2, coronary heart disease, susceptibility to, 4, autoimmune disease, susceptibility to, 2, autoimmune disease, susceptibility to, 3, systemic lupus erythematosus, susceptibility to, 4, myocardial infarction, susceptibility to, major depressive disorder 1, legionnaire disease, susceptibility to, myocardial infarction, susceptibility to, 2, major depressive disorder 2, hypertension, essential, susceptibility to, 4, epilepsy, idiopathic generalized, susceptibility to, 3, myoclonic epilepsy, juvenile, susceptibility to, 3, orofacial cleft 6, susceptibility to, coronary heart disease, susceptibility to, 5, attention deficit-hyperactivity disorder, susceptibility to, 1, attention deficit-hyperactivity disorder, susceptibility to, 2, attention deficit-hyperactivity disorder, susceptibility to, 3, attention deficit-hyperactivity disorder, susceptibility to, 4, Alzheimer disease 9, susceptibility to respiratory infections associated with CD8alpha chain mutation, dyslexia, susceptibility to, 8, autoimmune disease, susceptibility to, 4, hepatitis C virus, susceptibility to, epilepsy, idiopathic generalized, susceptibility to, 4, celiac disease, susceptibility to, 4, celiac disease, susceptibility to, 2, celiac disease, susceptibility to, 3, leprosy, susceptibility to, 1, systemic lupus erythematosus, susceptibility to, 5, systemic lupus erythematosus, susceptibility to, 6, opioid dependence, susceptibility to, 1, systemic lupus erythematosus, susceptibility to, 7, systemic lupus erythematosus, susceptibility to, 8, hypertension, essential, susceptibility to, 5, hypertension, essential, susceptibility to, 6, Parkinson disease 13, autosomal dominant, susceptibility to, West Nile virus, susceptibility to, hepatitis B virus, susceptibility to, Buruli ulcer, susceptibility to, osteoarthritis susceptibility 4, systemic lupus erythematosus, susceptibility to, 9, coronary heart disease, susceptibility to, 7, hypertension, essential, susceptibility to, 7, leprosy, susceptibility to, 4, hypertension, essential, susceptibility to, 8, epilepsy, idiopathic generalized, susceptibility to, 13, coronary heart disease, susceptibility to, 8, myoclonic epilepsy, juvenile, susceptibility to, 4, susceptibility to visceral leishmaniasis, 2, susceptibility to visceral leishmaniasis, 3, celiac disease, susceptibility to, 6, epilepsy, idiopathic generalized, susceptibility to, 5, epilepsy, childhood absence, susceptibility to, 6, celiac disease, susceptibility to, 7, celiac disease, susceptibility to, 8, celiac disease, susceptibility to, 9, celiac disease, susceptibility to, 10, celiac disease, susceptibility to, 11, celiac disease, susceptibility to, 12, celiac disease, susceptibility to, 13, coronary heart disease, susceptibility to, 9, systemic lupus erythematosus, susceptibility to, 10, systemic lupus erythematosus, susceptibility to, 11, systemic lupus erythematosus, susceptibility to, 12, epilepsy, childhood absence, susceptibility to, 5, attention deficit-hyperactivity disorder, susceptibility to, 5, attention deficit-hyperactivity disorder, susceptibility to, 6, systemic lupus erythematosus, susceptibility to, 13, sarcoidosis, susceptibility to, 2, sarcoidosis, susceptibility to, 3, osteoarthritis susceptibility 5, osteoarthritis susceptibility 6, focal segmental glomerulosclerosis 4, susceptibility to, epilepsy, idiopathic generalized, susceptibility to, 8, herpes simplex encephalitis, susceptibility to, 2, attention deficit-hyperactivity disorder, susceptibility to, 7, epilepsy, idiopathic generalized, susceptibility to, 10, pelvic organ prolapse, susceptibility to, 2, systemic lupus erythematosus, susceptibility to, 14, leprosy, susceptibility to, 5, thyrotoxic periodic paralysis, susceptibility to, 2, hearing loss, cisplatin-induced, susceptibility to, susceptibility to mononeuropathy of the median nerve, mild, fatty liver disease, nonalcoholic, susceptibility to, 2, leprosy, susceptibility to, 6, autoimmune disease, susceptibility to, 6, Parkinson disease 5, autosomal dominant, susceptibility to, aspergillosis, susceptibility to, sick sinus syndrome 3, susceptibility to, Parkinson disease 18, autosomal dominant, susceptibility to, epilepsy, juvenile myoclonic, susceptibility to, 9, dengue virus, susceptibility to, coronary heart disease, susceptibility to, 6, podoconiosis, susceptibility to, peripartum cardiomyopathy, susceptibility to, influenza, severe, susceptibility to, thyrotoxic periodic paralysis, susceptibility to, 3, human herpesvirus 8, susceptibility to, epilepsy, idiopathic generalized, susceptibility to, 12, herpes simplex encephalitis, susceptibility to, 3, herpes simplex encephalitis, susceptibility to, 4, pulmonary hypertension, neonatal, susceptibility to, craniosynostosis 5, susceptibility to, melioidosis, susceptibility to, chronic mountain sickness, susceptibility to, herpes simplex encephalitis, susceptibility to, 7, epilepsy, idiopathic generalized, susceptibility to, 14, hereditary neoplastic syndrome, autosomal recessive Mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR1 deficiency, autosomal recessive Mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR2 deficiency, susceptibility to localized juvenile periodontitis, inherited susceptibility to mycobacterial diseases, neural tube defects, susceptibility to, multiple system atrophy 1, susceptibility to, nephrolithiasis susceptibility caused by SLC26A1, myoclonic epilepsy, juvenile, susceptibility to, 1, epilepsy, childhood absence, susceptibility to, 1, autism, susceptiblity to, susceptibility to visceral leishmaniasis, 1, malaria, susceptibility to, spondyloarthropathy, susceptibility to, herpes simplex encephalitis, susceptibility to, 1, epilepsy, idiopathic generalized, susceptibility to, 18, epilepsy, idiopathic generalized, susceptibility to, 15, hepatitis, fulminant viral, susceptibility to, epilepsy, idiopathic generalized, susceptibility to, 16, autosomal recessive mendelian susceptibility to mycobacterial diseases due to partial jak1 deficiency, aortic aneurysm, familial thoracic 11, susceptibility to, craniosynostosis 7, amyotrophic lateral sclerosis, susceptibility to, 24, amyotrophic lateral sclerosis, susceptibility to, 25, epilepsy, juvenile myoclonic, susceptibility to, 10, susceptibility to angioedema induced by ACE inhibitors, epidermodysplasia verruciformis, susceptibility to, exfoliation syndrome, susceptibility to, basal cell carcinoma, susceptibility to, graft-versus-host disease, susceptibility to, narcolepsy, susceptibility to, pulmonary disease, chronic obstructive, susceptibility to, restless legs syndrome, susceptibility to, psoriasis, susceptibility to, age related macular degeneration, susceptibility to, allergic rhinitis, susceptibility to, dermatitis, atopic, susceptibility to, Hirschsprung disease, susceptibility to, diabetes mellitus, ketosis-prone, schizophrenia, susceptibility to, radioulnar synostosis, nonsyndromic, susceptibility to, lumbar disk herniation, susceptibility to, lumbar disk degeneration, susceptibility to, psoriatic arthritis, susceptibility to, migraine with or without aura, susceptibility to, Alzheimer disease, susceptibility to, mitochondrial, Asperger syndrome, susceptibility to, tobacco addiction, susceptibility to, lipodystrophy, partial, acquired, susceptibility to, Graves disease, susceptibility to, 1, epilepsy, idiopathic generalized, susceptibility to, 17, breast-ovarian cancer, familial, susceptibility to, blepharospasm, benign essential, susceptibility to, hemorrhage, intracerebral, susceptibility to, IgA nephropathy, susceptibility to, hemolytic uremic syndrome, atypical, susceptibility to, 7, vitiligo-associated multiple autoimmune disease susceptibility 6, delayed sleep phase syndrome, susceptibility to, encephalitis, acute, infection-induced, susceptibility to, malignant hyperthermia, susceptibility to, multicentric Castleman disease, susceptibility to, pelvic organ prolapse, susceptibility to, 1, amyotrophic lateral sclerosis, susceptibility to, 13, Graves disease, susceptibility to, X-linked 2, autoimmune thyroid disease, susceptibility to, 5, atrioventricular septal defect, susceptibility to, 1, epilepsy, juvenile myoclonic, susceptibility to, 6, autoimmune disease, susceptibility to, 5, epilepsy, idiopathic generalized, susceptibility to, 6, seasonal affective disorder, susceptibility to, ventricular fibrillation during myocardial infarction, susceptibility to, UV-induced skin damage, susceptibility to, antisocial behavior, susceptibility to, aplastic anemia, susceptibility to, cardiomyopathy, familial hypertrophic, 4, susceptibility to, cirrhosis, noncryptogenic, susceptibility to, coronary artery disease, severe, susceptibility to, dengue fever, susceptibility to, dengue hemorrhagic fever, susceptibility to, dengue shock syndrome, susceptibility to, dyslexia, susceptibility to, 4, dyslexia, susceptibility to, 7, efavirenz central nervous system toxicity, susceptibility to, obesity, susceptibility to, bleeding disorder, platelet-type, 13, susceptibility to, Schistosoma mansoni infection, susceptibility/resistance to, Parkinson disease 24, autosomal dominant, susceptibility to, iron overload, susceptibility to, hydrocephalus, congenital, 5, susceptibility to, hearing loss, noise-induced, susceptibility to, hyperemesis gravidarum, susceptibility to, Parkinson disease 26, autosomal dominant, susceptibility to, epilepsy, idiopathic generalized, susceptibility to, 19, polycystic kidney disease 9, susceptibility to, rhabdomyolysis, susceptibility to, scoliosis, isolated, susceptibility to, dystonia 38, susceptibility to, gallbladder disease 4, epilepsy, juvenile absence, susceptibility to, GBA1-related Parkinson disease, susceptibility, SH2B3-related immune system disorder

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

114 retrieved; paginated sample, class counts are floors:

40 uncertain significance, 40 likely benign, 13 benign, 8 conflicting classifications of pathogenicity, 6 benign/likely benign, 3 pathogenic, 2 risk factor, 2 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
3720341	NM_001077415.3(CRELD1):c.671_672insAAAC (p.Glu225fs)	CRELD1	Pathogenic	criteria provided, single submitter
465835	NM_001077415.3(CRELD1):c.523C>T (p.Arg175Ter)	CRELD1	Pathogenic	criteria provided, single submitter
861074	NM_001077415.3(CRELD1):c.1048+417_1048+418del	CRELD1	Pathogenic	criteria provided, single submitter
3666935	NM_001077415.3(CRELD1):c.913+1G>A	CRELD1	Likely pathogenic	criteria provided, single submitter
633463	NM_001077415.3(CRELD1):c.822_823del (p.Ala275fs)	CRELD1	Likely pathogenic	criteria provided, single submitter
3430	NM_001077415.3(CRELD1):c.484C>G (p.Pro162Ala)	CRELD1	risk factor	no assertion criteria provided
3431	NM_001077415.3(CRELD1):c.1240G>A (p.Glu414Lys)	CRELD1	risk factor	no assertion criteria provided
1165985	NM_001077415.3(CRELD1):c.659G>A (p.Arg220Gln)	CRELD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1305555	NM_001077415.3(CRELD1):c.699G>C (p.Lys233Asn)	CRELD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1522151	NM_001077415.3(CRELD1):c.566del (p.Gly189fs)	CRELD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
238218	NM_001077415.3(CRELD1):c.575G>A (p.Cys192Tyr)	CRELD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3429	NM_001077415.3(CRELD1):c.320G>A (p.Arg107His)	CRELD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
546928	NM_001077415.3(CRELD1):c.959del (p.Gln320fs)	CRELD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
841606	NM_001077415.3(CRELD1):c.796dup (p.Glu266fs)	CRELD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
930822	NM_001077415.3(CRELD1):c.658C>T (p.Arg220Ter)	CRELD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1373390	NC_000003.11:g.(?7782024)(11078652_?)dup	ARPC4	Uncertain significance	criteria provided, single submitter
830761	NC_000003.12:g.(?9701780)(9944589_?)dup	ARPC4	Uncertain significance	criteria provided, single submitter
1007012	NC_000003.11:g.(?9976103)(10191669_?)del	BRK1	Uncertain significance	criteria provided, single submitter
1002300	NM_001077415.3(CRELD1):c.1049-323G>A	CRELD1	Uncertain significance	criteria provided, single submitter
1397145	NM_001077415.3(CRELD1):c.979G>A (p.Gly327Ser)	CRELD1	Uncertain significance	criteria provided, single submitter
1397618	NM_001077415.3(CRELD1):c.1000G>A (p.Glu334Lys)	CRELD1	Uncertain significance	criteria provided, single submitter
1408913	NM_001077415.3(CRELD1):c.1049-401C>T	CRELD1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1427379	NM_001077415.3(CRELD1):c.1049-289G>A	CRELD1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1433113	NM_001077415.3(CRELD1):c.1049-368C>G	CRELD1	Uncertain significance	criteria provided, single submitter
1480454	NM_001077415.3(CRELD1):c.562G>A (p.Gly188Arg)	CRELD1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1484998	NM_001077415.3(CRELD1):c.1049-283C>T	CRELD1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1499992	NM_001077415.3(CRELD1):c.613A>G (p.Asn205Asp)	CRELD1	Uncertain significance	criteria provided, single submitter
1518524	NM_001077415.3(CRELD1):c.80T>G (p.Ile27Ser)	CRELD1	Uncertain significance	criteria provided, single submitter
1686601	NM_001077415.3(CRELD1):c.857C>G (p.Pro286Arg)	CRELD1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1698941	NM_001077415.3(CRELD1):c.565G>A (p.Gly189Ser)	CRELD1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 4 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
CRELD1	Limited	Autosomal dominant	atrioventricular septal defect, susceptibility to, 2	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CRELD1	Orphanet:576235	Partial atrioventricular septal defect without ventricular hypoplasia
CRELD1	Orphanet:99067	Complete atrioventricular septal defect with ventricular hypoplasia
CRELD1	Orphanet:99068	Complete atrioventricular septal defect-tetralogy of Fallot
ARPC4	Orphanet:662762	Motor delay-microcephaly-speech impairment-ocular abnormalities syndrome

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CRELD1	HGNC:14630	ENSG00000163703	Q96HD1	Protein disulfide isomerase CRELD1	gencc,clinvar
BRK1	HGNC:23057	ENSG00000254999	Q8WUW1	Protein BRICK1	clinvar
ARPC4	HGNC:707	ENSG00000241553	P59998	Actin-related protein 2/3 complex subunit 4	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CRELD1	Protein disulfide isomerase CRELD1	Protein disulfide isomerase.
BRK1	Protein BRICK1	Involved in regulation of actin and microtubule organization.
ARPC4	Actin-related protein 2/3 complex subunit 4	Actin-binding component of the Arp2/3 complex, a multiprotein complex that mediates actin polymerization upon stimulation by nucleation-promoting factor (NPF).

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 3 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	3	1.8×	0.174

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CRELD1	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, EGF-like_Ca-bd_dom
BRK1	Other/Unknown	no		BRICK1
ARPC4	Other/Unknown	no		ARPC4, ARPC2/4

Expression context

Cohort genes with no expression data: 0.

3 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1
adult organism	1
sperm	1
upper arm skin	1
granulocyte	1
leukocyte	1
monocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CRELD1	134	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
BRK1	256	ubiquitous	marker	sperm, upper arm skin, adult organism
ARPC4	290	ubiquitous	marker	monocyte, granulocyte, leukocyte

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BRK1	1,680
ARPC4	1,409
CRELD1	1,018

Intra-cohort edges

A	B	Sources
ARPC4	BRK1	string_interaction

Structural data

PDB: 2 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
BRK1	Q8WUW1	5
ARPC4	P59998	5

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CRELD1	Q96HD1	81.68

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 31. Enrichment computed across 3 evidence-associated genes (2 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Parasite infection	2	346.1×	1e-04	BRK1, ARPC4
Leishmania phagocytosis	2	346.1×	1e-04	BRK1, ARPC4
RHO GTPases Activate WASPs and WAVEs	2	317.2×	1e-04	BRK1, ARPC4
Fcgamma receptor (FCGR) dependent phagocytosis	2	278.5×	1e-04	BRK1, ARPC4
FCGR3A-mediated phagocytosis	2	187.2×	1e-04	BRK1, ARPC4
Regulation of actin dynamics for phagocytic cup formation	2	184.2×	1e-04	BRK1, ARPC4
Leishmania infection	2	163.1×	1e-04	BRK1, ARPC4
Parasitic Infection Pathways	2	163.1×	1e-04	BRK1, ARPC4
RHO GTPase Effectors	2	68.0×	7e-04	BRK1, ARPC4
Signaling by Rho GTPases	2	34.2×	0.003	BRK1, ARPC4
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	2	33.5×	0.003	BRK1, ARPC4
Innate Immune System	2	25.5×	0.004	BRK1, ARPC4
Infectious disease	2	24.8×	0.004	BRK1, ARPC4
Disease	2	13.1×	0.012	BRK1, ARPC4
Immune System	2	13.0×	0.012	BRK1, ARPC4
EPHB-mediated forward signaling	1	132.8×	0.015	ARPC4
Signaling by VEGF	1	109.8×	0.017	BRK1
Signal Transduction	2	10.2×	0.017	BRK1, ARPC4
EPH-Ephrin signaling	1	82.8×	0.020	ARPC4
VEGFA-VEGFR2 Pathway	1	69.6×	0.022	BRK1
RAC2 GTPase cycle	1	63.4×	0.023	BRK1
RAC3 GTPase cycle	1	59.5×	0.024	BRK1
Clathrin-mediated endocytosis	1	42.6×	0.031	ARPC4
RAC1 GTPase cycle	1	30.5×	0.041	BRK1
RHO GTPase cycle	1	30.1×	0.041	BRK1
Signaling by Receptor Tyrosine Kinases	1	25.8×	0.046	BRK1
Axon guidance	1	22.6×	0.050	ARPC4
Nervous system development	1	21.5×	0.051	ARPC4
Membrane Trafficking	1	18.5×	0.057	ARPC4
Vesicle-mediated transport	1	17.4×	0.059	ARPC4

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of actin polymerization or depolymerization	1	936.2×	0.006	BRK1
positive regulation of Arp2/3 complex-mediated actin nucleation	1	702.2×	0.006	BRK1
actin nucleation	1	624.1×	0.006	ARPC4
cardiac septum development	1	561.7×	0.006	CRELD1
endocardial cushion development	1	468.1×	0.006	CRELD1
Arp2/3 complex-mediated actin nucleation	1	351.1×	0.007	ARPC4
positive regulation of lamellipodium assembly	1	200.6×	0.010	BRK1
Rac protein signal transduction	1	187.2×	0.010	BRK1
actin filament polymerization	1	160.5×	0.010	ARPC4
cell motility	1	133.8×	0.010	BRK1
fibroblast proliferation	1	130.6×	0.010	BRK1
positive regulation of protein-containing complex assembly	1	112.3×	0.011	BRK1
positive regulation of fibroblast proliferation	1	98.5×	0.012	BRK1
actin filament organization	1	39.6×	0.027	BRK1
in utero embryonic development	1	24.0×	0.041	BRK1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 3

Druggability breadth: 2 of 3 evidence-associated genes (67%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CRELD1	0	0
BRK1	0	0
ARPC4	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
ARPC4	7	Binding:7
BRK1	1	Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	3	CRELD1, BRK1, ARPC4

Undrugged target profiles

3 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
CRELD1	0	—
BRK1	1	—
ARPC4	7	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.