Hematuria, benign familial, 1

Summary

Hematuria, benign familial, 1 (MONDO:0007709) is a disease caused by variants in COL4A3 and COL4A4, with 4 cohort genes.

At a glance

• Causal genes: COL4A3 (GenCC Strong), COL4A4 (GenCC Strong)
• Cohort genes: 4
• ClinVar variants: 535

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hematuria, benign familial, 1
Mondo ID	MONDO:0007709
OMIM	141200
Is cancer (heuristic)	no

Also known as: BFH · hematuria, benign familial · hematuria, familial benign

Data availability: 535 ClinVar variants · 5 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › hematuria, benign familial › hematuria, benign familial, 1

Related subtypes (1): hematuria, benign familial, 2

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

535 retrieved; paginated sample, class counts are floors:

163 uncertain significance, 145 conflicting classifications of pathogenicity, 140 likely pathogenic, 67 pathogenic/likely pathogenic, 19 pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1029644	NM_000092.5(COL4A4):c.3214+1G>T	COL4A4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1066915	NM_000092.5(COL4A4):c.559-2A>G	COL4A4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1067311	NM_000092.5(COL4A4):c.193-2A>C	COL4A4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1074209	NM_000092.5(COL4A4):c.3310_3313dup (p.Gln1105fs)	COL4A4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1075428	NM_000092.5(COL4A4):c.4953G>A (p.Trp1651Ter)	COL4A4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1179086	NM_000092.5(COL4A4):c.3882_3883del (p.Cys1294fs)	COL4A4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1219193	NM_000092.5(COL4A4):c.1145G>C (p.Gly382Ala)	COL4A4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1333646	NM_000092.5(COL4A4):c.2869G>A (p.Gly957Arg)	COL4A4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1346806	NM_000092.5(COL4A4):c.559-2A>T	COL4A4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1400565	NM_000092.5(COL4A4):c.3514G>T (p.Gly1172Ter)	COL4A4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1438858	NM_000092.5(COL4A4):c.2251G>T (p.Gly751Ter)	COL4A4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1453657	NM_000092.5(COL4A4):c.1099G>A (p.Gly367Ser)	COL4A4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1456812	NM_000092.5(COL4A4):c.2029G>A (p.Gly677Ser)	COL4A4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1480342	NM_000092.5(COL4A4):c.3488G>A (p.Gly1163Asp)	COL4A4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1496666	NM_000092.5(COL4A4):c.930+1G>A	COL4A4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1695007	NM_000092.5(COL4A4):c.2435_2436del (p.Glu812fs)	COL4A4	Pathogenic	criteria provided, multiple submitters, no conflicts
1699904	NM_000092.5(COL4A4):c.941G>A (p.Gly314Asp)	COL4A4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
17406	NM_000092.5(COL4A4):c.2690G>A (p.Gly897Glu)	COL4A4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
17407	NM_000092.5(COL4A4):c.4129C>T (p.Arg1377Ter)	COL4A4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
17410	NM_000092.5(COL4A4):c.3222dup (p.Gly1075fs)	COL4A4	Pathogenic	no assertion criteria provided
17411	NM_000092.5(COL4A4):c.2878G>C (p.Gly960Arg)	COL4A4	Pathogenic	no assertion criteria provided
1804099	NM_000092.5(COL4A4):c.2383+1G>A	COL4A4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1985757	NM_000092.5(COL4A4):c.4079del (p.Pro1360fs)	COL4A4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2008694	NM_000092.5(COL4A4):c.93_94del (p.Ser32fs)	COL4A4	Pathogenic	criteria provided, multiple submitters, no conflicts
2009206	NM_000092.5(COL4A4):c.292_293dup (p.Pro99fs)	COL4A4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2019277	NM_000092.5(COL4A4):c.3331C>T (p.Gln1111Ter)	COL4A4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2067966	NM_000092.5(COL4A4):c.1022G>A (p.Gly341Asp)	COL4A4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2105703	NM_000092.5(COL4A4):c.2616del (p.Gly873fs)	COL4A4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2133804	NM_000092.5(COL4A4):c.1169del (p.Pro390fs)	COL4A4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2180806	NM_000092.5(COL4A4):c.666_667insA (p.Gly223fs)	COL4A4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 23 · Orphanet: 10 · 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
COL4A3	Strong	Autosomal dominant	hematuria, benign familial, 1	12
COL4A4	Strong	Autosomal dominant	hematuria, benign familial, 1	11

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
COL4A3	Orphanet:653722	Digenic Alport syndrome
COL4A3	Orphanet:656	Hereditary steroid-resistant nephrotic syndrome
COL4A3	Orphanet:88918	Autosomal dominant Alport syndrome
COL4A3	Orphanet:88919	Autosomal recessive Alport syndrome
COL4A4	Orphanet:653722	Digenic Alport syndrome
COL4A4	Orphanet:88918	Autosomal dominant Alport syndrome
COL4A4	Orphanet:88919	Autosomal recessive Alport syndrome
CPLANE1	Orphanet:2754	Orofaciodigital syndrome type 6
CPLANE1	Orphanet:475	Isolated Joubert syndrome
CPLANE1	Orphanet:65684	Monomelic amyotrophy

Cohort genes → proteins

4 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
COL4A3	HGNC:2204	ENSG00000169031	Q01955	Collagen alpha-3(IV) chain	gencc,clinvar
COL4A4	HGNC:2206	ENSG00000081052	P53420	Collagen alpha-4(IV) chain	gencc,clinvar
CPLANE1	HGNC:25801	ENSG00000197603	Q9H799	Ciliogenesis and planar polarity effector 1	clinvar
MFF-DT	HGNC:41067	ENSG00000236432		MFF divergent transcript	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
COL4A3	Collagen alpha-3(IV) chain	Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a ‘chicken-wire’ meshwork together with laminins, proteoglycans and entactin/nidogen.
COL4A4	Collagen alpha-4(IV) chain	Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a ‘chicken-wire’ meshwork together with laminins, proteoglycans and entactin/nidogen.
CPLANE1	Ciliogenesis and planar polarity effector 1	Involved in ciliogenesis.

Protein-family classification

Druggable: 0 · Difficult: 1 · 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
Scaffold/PPI	1	4.3×	0.404
Other/Unknown	3	1.3×	0.404

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
COL4A3	Other/Unknown	no		Collagen_IV_NC, Collagen, CTDL_fold
COL4A4	Other/Unknown	no		Collagen_IV_NC, Collagen, CTDL_fold
CPLANE1	Scaffold/PPI	no		CPLANE1, WD40_repeat_dom_sf
MFF-DT	Other/Unknown	no

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
pigmented layer of retina	2
male germ line stem cell (sensu Vertebrata) in testis	2
retina	1
skeletal muscle tissue of biceps brachii	1
metanephros cortex	1
renal medulla	1
calcaneal tendon	1
sural nerve	1
bone marrow cell	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
COL4A3	233	broad	marker	skeletal muscle tissue of biceps brachii, pigmented layer of retina, retina
COL4A4	187	broad	marker	renal medulla, metanephros cortex, pigmented layer of retina
CPLANE1	195	ubiquitous	marker	sural nerve, calcaneal tendon, male germ line stem cell (sensu Vertebrata) in testis
MFF-DT	158		yes	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, bone marrow cell

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
COL4A3	1,671
COL4A4	1,243
CPLANE1	439
MFF-DT	0

Intra-cohort edges

A	B	Sources
COL4A3	COL4A4	string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
COL4A3	Q01955	2
COL4A4	P53420	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CPLANE1	Q9H799

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 14. Enrichment computed across 4 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
Anchoring fibril formation	2	761.3×	1e-05	COL4A3, COL4A4
Fibronectin matrix formation	2	571.0×	1e-05	COL4A3, COL4A4
Crosslinking of collagen fibrils	2	571.0×	1e-05	COL4A3, COL4A4
Attachment of bacteria to epithelial cells	2	496.5×	1e-05	COL4A3, COL4A4
Laminin interactions	2	380.7×	2e-05	COL4A3, COL4A4
Collagen chain trimerization	2	259.6×	3e-05	COL4A3, COL4A4
Signaling by PDGF	2	253.8×	3e-05	COL4A3, COL4A4
NCAM1 interactions	2	248.3×	3e-05	COL4A3, COL4A4
Assembly of collagen fibrils and other multimeric structures	2	200.3×	4e-05	COL4A3, COL4A4
Collagen degradation	2	175.7×	4e-05	COL4A3, COL4A4
Collagen biosynthesis and modifying enzymes	2	170.4×	4e-05	COL4A3, COL4A4
Non-integrin membrane-ECM interactions	2	154.3×	5e-05	COL4A3, COL4A4
ECM proteoglycans	2	150.3×	5e-05	COL4A3, COL4A4
Integrin cell surface interactions	2	134.3×	5e-05	COL4A3, COL4A4

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
glomerular basement membrane development	2	1021.3×	1e-05	COL4A3, COL4A4
collagen fibril organization	2	149.8×	3e-04	COL4A3, COL4A4
negative regulation of vascular endothelial cell proliferation	1	1123.5×	0.003	COL4A3
collagen-activated tyrosine kinase receptor signaling pathway	1	432.1×	0.005	COL4A3
endothelial cell apoptotic process	1	432.1×	0.005	COL4A3
negative regulation of angiogenesis	1	56.2×	0.032	COL4A3
sensory perception of sound	1	33.6×	0.046	COL4A3
cilium assembly	1	24.5×	0.055	CPLANE1
cell surface receptor signaling pathway	1	21.4×	0.056	COL4A3
negative regulation of cell population proliferation	1	14.0×	0.076	COL4A3
cell adhesion	1	12.5×	0.078	COL4A3

Therapeutics

Drug target analysis

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

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

Top cohort targets by molecule count

Symbol	Molecules	Max phase
COL4A3	0	0
COL4A4	0	0
CPLANE1	0	0
MFF-DT	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	4	COL4A3, COL4A4, CPLANE1, MFF-DT

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
COL4A3	0	—
COL4A4	0	—
CPLANE1	0	—
MFF-DT	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.