congenital bilateral aplasia of vas deferens from CFTR mutation

Summary

congenital bilateral aplasia of vas deferens from CFTR mutation (MONDO:0010178) is a disease with 4 cohort genes and 2 clinical trials. Top therapeutic interventions include evogliptin.

At a glance

• Cohort genes: 4
• ClinVar variants: 499
• Clinical trials: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	congenital bilateral aplasia of vas deferens from CFTR mutation
Mondo ID	MONDO:0010178
OMIM	277180
DOID	DOID:0111864
NCIT	C129303
UMLS	C0403814
MedGen	98021
GARD	0015243
Is cancer (heuristic)	no

Also known as: CAVD · CBAVD · congenital bilateral absence of vas deferens · congenital bilateral aplasia of the vas deferens · vas deferens, congenital bilateral aplasia of

Data availability: 499 ClinVar variants · 3 cell lines.

Disease family

Classification path: disease › human disease › disease by body system or component › reproductive system disorder › male reproductive system disorder › congenital bilateral absence of vas deferens › congenital bilateral aplasia of vas deferens from CFTR mutation

Related subtypes (2): vas deferens, congenital bilateral aplasia of, X-linked, vas deferens, congenital unilateral aplasia of

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

499 retrieved; paginated sample, class counts are floors:

183 pathogenic, 119 conflicting classifications of pathogenicity, 93 uncertain significance, 62 pathogenic/likely pathogenic, 15 likely pathogenic, 14 pathogenic; drug response, 8 drug response, 2 benign/likely benign, 1 pathogenic/likely pathogenic; other, 1 benign, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
253013	NM_001079858.3(ADGRG2):c.2845del (p.Cys949fs)	ADGRG2	Pathogenic	criteria provided, single submitter
253014	NM_001079858.3(ADGRG2):c.2002_2006delinsAGA (p.Leu668fs)	ADGRG2	Pathogenic	criteria provided, single submitter
253015	NM_001079858.3(ADGRG2):c.1545dup (p.Glu516Ter)	ADGRG2	Pathogenic	criteria provided, single submitter
691628	NM_001079858.3(ADGRG2):c.2473C>T (p.Arg825Ter)	ADGRG2	Pathogenic	criteria provided, single submitter
691629	NM_001079858.3(ADGRG2):c.2096dup (p.Phe700fs)	ADGRG2	Pathogenic	criteria provided, single submitter
691630	NM_001079858.3(ADGRG2):c.251C>G (p.Ser84Ter)	ADGRG2	Pathogenic	criteria provided, single submitter
691631	NM_001079858.3(ADGRG2):c.1460del (p.Gly487fs)	ADGRG2	Pathogenic	criteria provided, single submitter
691632	NM_001079858.3(ADGRG2):c.1013del (p.Pro338fs)	ADGRG2	Pathogenic	criteria provided, single submitter
691633	NM_001079858.3(ADGRG2):c.1731_1839+373del	ADGRG2	Pathogenic	criteria provided, single submitter
1177286	NM_000492.4(CFTR):c.1132C>T (p.Gln378Ter)	CFTR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1706049	NM_000492.4(CFTR):c.498del (p.Lys166fs)	CFTR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1706055	NM_000492.4(CFTR):c.777del (p.Leu259_Val260insTer)	CFTR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1706061	NM_000492.4(CFTR):c.3930G>A (p.Trp1310Ter)	CFTR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
178713	NM_000492.4(CFTR):c.1210-11T>G	CFTR	Pathogenic/Likely pathogenic; other	criteria provided, multiple submitters, no conflicts
188783	NM_000492.4(CFTR):c.3368-2A>G	CFTR	Pathogenic	reviewed by expert panel
188958	NM_000492.4(CFTR):c.1327_1330dup (p.Ile444fs)	CFTR	Pathogenic	reviewed by expert panel
2503929	NM_000492.4(CFTR):c.4408G>T (p.Glu1470Ter)	CFTR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2691445	NM_000492.4(CFTR):c.1972dup (p.Arg658fs)	CFTR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3241145	NM_000492.4(CFTR):c.53+1G>C	CFTR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
35821	NM_000492.4(CFTR):c.1367T>C (p.Val456Ala)	CFTR	Pathogenic	reviewed by expert panel
35822	NM_000492.4(CFTR):c.1397C>G (p.Ser466Ter)	CFTR	Pathogenic	reviewed by expert panel
35823	NM_000492.4(CFTR):c.1400T>C (p.Leu467Pro)	CFTR	Pathogenic	reviewed by expert panel
35824	NM_000492.4(CFTR):c.14C>T (p.Pro5Leu)	CFTR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
35829	NM_000492.4(CFTR):c.1673T>C (p.Leu558Ser)	CFTR	Pathogenic	reviewed by expert panel
35831	NM_000492.4(CFTR):c.1692del (p.Asp565fs)	CFTR	Pathogenic	reviewed by expert panel
35834	NM_000492.4(CFTR):c.1911del (p.Gln637fs)	CFTR	Pathogenic	reviewed by expert panel
35836	NM_000492.4(CFTR):c.2012del (p.Ser670_Leu671insTer)	CFTR	Pathogenic	reviewed by expert panel
35837	NM_000492.4(CFTR):c.2051_2052delinsG (p.Lys684fs)	CFTR	Pathogenic	reviewed by expert panel
35838	NM_000492.4(CFTR):c.2052dup (p.Gln685fs)	CFTR	Pathogenic	reviewed by expert panel
35846	NM_000492.4(CFTR):c.273+3A>C	CFTR	Pathogenic	reviewed by expert panel

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 7 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CFTR	Orphanet:399805	Male infertility with azoospermia or oligozoospermia due to single gene mutation
CFTR	Orphanet:48	Congenital bilateral absence of vas deferens
CFTR	Orphanet:498359	Aquagenic palmoplantar keratoderma
CFTR	Orphanet:586	Cystic fibrosis
CFTR	Orphanet:60033	Idiopathic bronchiectasis
CFTR	Orphanet:700124	Autosomal recessive hereditary chronic pancreatitis
ADGRG2	Orphanet:48	Congenital bilateral absence of vas deferens

Cohort genes → proteins

4 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CFTR	HGNC:1884	ENSG00000001626	P13569	Cystic fibrosis transmembrane conductance regulator	clinvar
CFTR-AS1	HGNC:40144	ENSG00000232661		CFTR antisense RNA 1	clinvar
CFTR-AS2	HGNC:40145	ENSG00000083622		CFTR antisense RNA 2	clinvar
ADGRG2	HGNC:4516	ENSG00000173698	Q8IZP9	Adhesion G-protein coupled receptor G2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CFTR	Cystic fibrosis transmembrane conductance regulator	Epithelial ion channel that plays an important role in the regulation of epithelial ion and water transport and fluid homeostasis.
ADGRG2	Adhesion G-protein coupled receptor G2	Adhesion G-protein coupled receptor (aGPCR) for steroid hormones, such as dehydroepiandrosterone (DHEA; also named 3beta-hydroxyandrost-5-en-17-one) and androstenedione.

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.5

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
Transporter	1	19.4×	0.151
GPCR	1	6.0×	0.235
Other/Unknown	2	0.9×	0.769

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CFTR	Transporter	yes	2.7.4.3	ABC_transporter-like_ATP-bd, AAA+_ATPase, CFTR/ABCC7
CFTR-AS1	Other/Unknown	no
CFTR-AS2	Other/Unknown	no
ADGRG2	GPCR	yes		GPS, GPCR_2_secretin-like, GPCR_2-like_7TM

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)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
body of pancreas	3
pancreas	3
gall bladder	1
islet of Langerhans	1
primordial germ cell in gonad	1
caput epididymis	1
corpus epididymis	1
parotid gland	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CFTR	193	broad	marker	body of pancreas, gall bladder, pancreas
CFTR-AS1	68		yes	body of pancreas, islet of Langerhans, pancreas
CFTR-AS2	94		marker	body of pancreas, pancreas, primordial germ cell in gonad
ADGRG2	182	broad	marker	corpus epididymis, caput epididymis, parotid gland

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CFTR	7,664
ADGRG2	723
CFTR-AS1	0
CFTR-AS2	0

Intra-cohort edges

A	B	Sources
ADGRG2	CFTR	string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CFTR	P13569	58

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ADGRG2	Q8IZP9	62.76

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 11. Enrichment computed across 4 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
RHO GTPases regulate CFTR trafficking	1	3806.7×	0.003	CFTR
Chaperone Mediated Autophagy	1	496.5×	0.008	CFTR
Late endosomal microautophagy	1	326.3×	0.008	CFTR
Aggrephagy	1	248.3×	0.008	CFTR
Developmental Lineage of Pancreatic Ductal Cells	1	228.4×	0.008	CFTR
Defective CFTR causes cystic fibrosis	1	219.6×	0.008	CFTR
RHOQ GTPase cycle	1	181.3×	0.009	CFTR
ABC-family protein mediated transport	1	121.5×	0.011	CFTR
Cargo recognition for clathrin-mediated endocytosis	1	104.8×	0.012	CFTR
Clathrin-mediated endocytosis	1	85.2×	0.013	CFTR
Ub-specific processing proteases	1	53.1×	0.019	CFTR

GO biological processes 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.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
intracellular pH elevation	1	2808.7×	0.005	CFTR
transepithelial water transport	1	1685.2×	0.005	CFTR
positive regulation of enamel mineralization	1	1685.2×	0.005	CFTR
membrane hyperpolarization	1	936.2×	0.005	CFTR
multicellular organismal-level water homeostasis	1	842.6×	0.005	CFTR
amelogenesis	1	702.2×	0.005	CFTR
cellular response to forskolin	1	561.7×	0.006	CFTR
water transport	1	495.6×	0.006	CFTR
bicarbonate transport	1	401.2×	0.006	CFTR
cholesterol transport	1	366.4×	0.006	CFTR
sperm capacitation	1	337.0×	0.006	CFTR
cholesterol biosynthetic process	1	210.7×	0.009	CFTR
cellular response to cAMP	1	145.3×	0.012	CFTR
chloride transmembrane transport	1	118.7×	0.014	CFTR
transmembrane transport	1	84.3×	0.017	CFTR
response to endoplasmic reticulum stress	1	83.4×	0.017	CFTR
establishment of localization in cell	1	80.2×	0.017	CFTR
spermatid development	1	72.6×	0.018	ADGRG2
phospholipase C-activating G protein-coupled receptor signaling pathway	1	65.8×	0.018	ADGRG2
adenylate cyclase-activating G protein-coupled receptor signaling pathway	1	56.5×	0.020	ADGRG2
cell surface receptor signaling pathway	1	32.0×	0.034	ADGRG2
G protein-coupled receptor signaling pathway	1	18.1×	0.056	ADGRG2
spermatogenesis	1	17.6×	0.056	ADGRG2

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 4 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
CFTR	IVACAFTOR

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CFTR	14	4
CFTR-AS1	0	0
CFTR-AS2	0	0
ADGRG2	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
IVACAFTOR	4	CFTR
LUMACAFTOR	4	CFTR
TEZACAFTOR	4	CFTR
ELEXACAFTOR	4	CFTR
GLYBURIDE	4	CFTR
RUTIN	3	CFTR
BAMOCAFTOR	3	CFTR
QUERCETIN	3	CFTR
GALICAFTOR	2	CFTR
GENISTEIN	2	CFTR
ICENTICAFTOR	2	CFTR
NAVOCAFTOR	2	CFTR
RISELCAFTOR	2	CFTR
GLPG-2737	2	CFTR

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
CFTR	520	Binding:497, Functional:17, ADMET:5, Toxicity:1
ADGRG2	2	Binding:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CFTR	2.7.4.3, 5.6.1.6	adenylate kinase, channel-conductance-controlling ATPase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
CFTR	520

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 1.

Cohort genes with a CPIC/DPWG dosing guideline

Symbol	CPIC guidelines
CFTR	1

Chemical tractability of cohort targets

14 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.

Compound	Max phase	Cohort target (bioactivity)
IVACAFTOR	4	CFTR
LUMACAFTOR	4	CFTR
TEZACAFTOR	4	CFTR
ELEXACAFTOR	4	CFTR
GLYBURIDE	4	CFTR
RUTIN	3	CFTR
BAMOCAFTOR	3	CFTR
QUERCETIN	3	CFTR
GALICAFTOR	2	CFTR
GENISTEIN	2	CFTR
ICENTICAFTOR	2	CFTR
NAVOCAFTOR	2	CFTR
RISELCAFTOR	2	CFTR
GLPG-2737	2	CFTR

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	CFTR
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	ADGRG2
E	Difficult family or no structure, no drug	2	CFTR-AS1, CFTR-AS2

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)
ADGRG2	2	CFTR
CFTR-AS1	0	—
CFTR-AS2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 2.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE4	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04521452	PHASE4	UNKNOWN	Randomized, Open-label Trial of Inhibitory Effect of Evogliptin on Progression of CAVD
NCT06045702	Not specified	RECRUITING	Establishment of a Primary Epididymal Cell Model From Epididymal Samples to Study CFTR Gene Regulation

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
EVOGLIPTIN	4	1