Hematuria, benign familial, 2

Summary

Hematuria, benign familial, 2 (MONDO:0958186) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 440

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hematuria, benign familial, 2
Mondo ID	MONDO:0958186
OMIM	620320
UMLS	C5830421
MedGen	1841057
Is cancer (heuristic)	no

Data availability: 440 ClinVar variants.

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, 2

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

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

440 retrieved; paginated sample, class counts are floors:

137 uncertain significance, 118 likely pathogenic, 109 conflicting classifications of pathogenicity, 56 pathogenic/likely pathogenic, 18 pathogenic, 2 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1070961	NM_000091.5(COL4A3):c.522dup (p.Leu175fs)	COL4A3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1375749	NM_000091.5(COL4A3):c.3619G>A (p.Gly1207Arg)	COL4A3	Pathogenic	criteria provided, multiple submitters, no conflicts
1410422	NM_000091.5(COL4A3):c.4265C>G (p.Ser1422Ter)	COL4A3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1441244	NM_000091.5(COL4A3):c.1132G>A (p.Gly378Arg)	COL4A3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1455985	NM_000091.5(COL4A3):c.4001G>A (p.Gly1334Glu)	COL4A3	Pathogenic	criteria provided, multiple submitters, no conflicts
1520952	NM_000091.5(COL4A3):c.4755+1G>A	COL4A3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
17484	NM_000091.5(COL4A3):c.4441C>T (p.Arg1481Ter)	COL4A3	Pathogenic	criteria provided, multiple submitters, no conflicts
17492	NM_000091.5(COL4A3):c.3499G>A (p.Gly1167Arg)	COL4A3	Pathogenic	criteria provided, multiple submitters, no conflicts
192299	NM_000091.5(COL4A3):c.40_63del (p.Leu14_Leu21del)	COL4A3	Pathogenic	criteria provided, multiple submitters, no conflicts
2093215	NM_000091.5(COL4A3):c.3737C>G (p.Ser1246Ter)	COL4A3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2105186	NM_000091.5(COL4A3):c.448del (p.Ala150fs)	COL4A3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
222053	NM_000091.5(COL4A3):c.765G>T (p.Thr255=)	COL4A3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2731165	NM_000091.5(COL4A3):c.1408+1G>C	COL4A3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3234059	NM_000091.5(COL4A3):c.4357C>T (p.Gln1453Ter)	COL4A3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3235248	NM_000091.5(COL4A3):c.716dup (p.Pro240fs)	COL4A3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3377030	NM_000091.5(COL4A3):c.3683G>A (p.Gly1228Asp)	COL4A3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3586030	NM_000091.5(COL4A3):c.1820del (p.Pro607fs)	COL4A3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3586038	NM_000091.5(COL4A3):c.2008C>T (p.Gln670Ter)	COL4A3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3586074	NM_000091.5(COL4A3):c.2980+2T>G	COL4A3	Pathogenic	criteria provided, single submitter
3586120	NM_000091.5(COL4A3):c.3620G>T (p.Gly1207Val)	COL4A3	Pathogenic	criteria provided, single submitter
369964	NM_000091.5(COL4A3):c.2083G>A (p.Gly695Arg)	COL4A3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
371669	NM_000091.5(COL4A3):c.1918G>A (p.Gly640Arg)	COL4A3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
430020	NM_000091.5(COL4A3):c.1184G>A (p.Gly395Glu)	COL4A3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
438655	NM_000091.5(COL4A3):c.3546_3548dup (p.Gly1183dup)	COL4A3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
447168	NM_000091.5(COL4A3):c.2126G>A (p.Gly709Glu)	COL4A3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
447169	NM_000091.5(COL4A3):c.2452G>A (p.Gly818Arg)	COL4A3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
447171	NM_000091.5(COL4A3):c.3250G>T (p.Glu1084Ter)	COL4A3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
451439	NM_000091.5(COL4A3):c.3882+5G>A	COL4A3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
495548	NM_000091.5(COL4A3):c.1216C>T (p.Arg406Ter)	COL4A3	Pathogenic	criteria provided, multiple submitters, no conflicts
522482	NM_000091.5(COL4A3):c.1855G>A (p.Gly619Arg)	COL4A3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

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

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

Cohort genes → proteins

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
COL4A3	HGNC:2204	ENSG00000169031	Q01955	Collagen alpha-3(IV) chain	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.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

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

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
pigmented layer of retina	1
retina	1
skeletal muscle tissue of biceps brachii	1
bone marrow cell	1
male germ line stem cell (sensu Vertebrata) in testis	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
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: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
COL4A3	1,671
MFF-DT	0

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
COL4A3	Q01955	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 14. Enrichment computed across 2 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
Anchoring fibril formation	1	761.3×	0.007	COL4A3
Fibronectin matrix formation	1	571.0×	0.007	COL4A3
Crosslinking of collagen fibrils	1	571.0×	0.007	COL4A3
Attachment of bacteria to epithelial cells	1	496.5×	0.007	COL4A3
Laminin interactions	1	380.7×	0.007	COL4A3
Collagen chain trimerization	1	259.6×	0.007	COL4A3
Signaling by PDGF	1	253.8×	0.007	COL4A3
NCAM1 interactions	1	248.3×	0.007	COL4A3
Assembly of collagen fibrils and other multimeric structures	1	200.3×	0.007	COL4A3
Collagen degradation	1	175.7×	0.007	COL4A3
Collagen biosynthesis and modifying enzymes	1	170.4×	0.007	COL4A3
Non-integrin membrane-ECM interactions	1	154.3×	0.007	COL4A3
ECM proteoglycans	1	150.3×	0.007	COL4A3
Integrin cell surface interactions	1	134.3×	0.007	COL4A3

GO biological processes 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.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of vascular endothelial cell proliferation	1	3370.4×	0.002	COL4A3
glomerular basement membrane development	1	1532.0×	0.002	COL4A3
collagen-activated tyrosine kinase receptor signaling pathway	1	1296.3×	0.002	COL4A3
endothelial cell apoptotic process	1	1296.3×	0.002	COL4A3
collagen fibril organization	1	224.7×	0.009	COL4A3
negative regulation of angiogenesis	1	168.5×	0.010	COL4A3
sensory perception of sound	1	100.9×	0.014	COL4A3
cell surface receptor signaling pathway	1	64.1×	0.020	COL4A3
negative regulation of cell population proliferation	1	42.1×	0.026	COL4A3
cell adhesion	1	37.5×	0.027	COL4A3

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 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
MFF-DT	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; 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	2	COL4A3, MFF-DT

Undrugged target profiles

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

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.