Heterotaxy, visceral, 7, autosomal

Summary

Heterotaxy, visceral, 7, autosomal (MONDO:0014762) is a disease caused by MMP21 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: MMP21 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 31

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	heterotaxy, visceral, 7, autosomal
Mondo ID	MONDO:0014762
OMIM	616749
DOID	DOID:0051021
UMLS	C4225217
MedGen	902629
GARD	0025014
Is cancer (heuristic)	no

Also known as: heterotaxy, visceral, 7, autosomal · heterotaxy, visceral, 7, autosomal; HTX7 · HTX7 · MMP21 visceral heterotaxy · visceral heterotaxy caused by mutation in MMP21

Data availability: 31 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › visceral heterotaxy › heterotaxy, visceral, 7, autosomal

Related subtypes (18): right atrial isomerism, situs inversus, heterotaxy, visceral, 1, X-linked, laterality defects, autosomal dominant, heterotaxy, visceral, 2, autosomal, heterotaxy, visceral, 3, autosomal, heterotaxy, visceral, 4, autosomal, heterotaxy, visceral, 6, autosomal, heterotaxy, visceral, 8, autosomal, dextrocardia, levocardia, heterotaxy, visceral, 9, autosomal, with male infertility, heterotaxy, visceral, 10, autosomal, with male infertility, heterotaxy, visceral, 11, autosomal, with male infertility, heterotaxy, visceral, 5, autosomal, heterotaxy, visceral, 12, autosomal, heterotaxy, visceral, 13, autosomal, heterotaxy, visceral, 14, autosomal

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

31 retrieved; paginated sample, class counts are floors:

11 uncertain significance, 9 pathogenic, 5 likely pathogenic, 3 pathogenic/likely pathogenic, 1 benign, 1 benign/likely benign, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
265317	NM_147191.1(MMP21):c.1372C>T (p.Arg458Ter)	MMP21	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
279945	NM_147191.1(MMP21):c.240dup (p.Lys81fs)	MMP21	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
289001	NM_147191.1(MMP21):c.1203G>A (p.Trp401Ter)	MMP21	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3235109	NM_147191.1(MMP21):c.1025_1026del (p.Lys342fs)	MMP21	Pathogenic	criteria provided, multiple submitters, no conflicts
3235111	NM_147191.1(MMP21):c.677T>C (p.Ile226Thr)	MMP21	Pathogenic	no assertion criteria provided
3235112	NM_147191.1(MMP21):c.365del (p.Met122fs)	MMP21	Pathogenic	no assertion criteria provided
3235113	NC_000010.11:g.125772345_125778250del	MMP21	Pathogenic	no assertion criteria provided
3235115	NM_147191.1(MMP21):c.961G>C (p.Ala321Pro)	MMP21	Pathogenic	no assertion criteria provided
3235117	NM_147191.1(MMP21):c.847C>T (p.His283Tyr)	MMP21	Pathogenic	no assertion criteria provided
3235118	NM_147191.1(MMP21):c.947G>A (p.Trp316Ter)	MMP21	Pathogenic	no assertion criteria provided
3235119	NM_147191.1(MMP21):c.854T>C (p.Ile285Thr)	MMP21	Pathogenic	no assertion criteria provided
3235120	NM_147191.1(MMP21):c.1380_1381del (p.Lys461fs)	MMP21	Pathogenic	no assertion criteria provided
2507421	NM_147191.1(MMP21):c.1303del (p.Ser435fs)	MMP21	Likely pathogenic	criteria provided, single submitter
3062262	NM_147191.1(MMP21):c.614G>A (p.Trp205Ter)	MMP21	Likely pathogenic	criteria provided, single submitter
3779882	NM_147191.1(MMP21):c.765dup (p.Gly256fs)	MMP21	Likely pathogenic	criteria provided, single submitter
545547	NM_147191.1(MMP21):c.643G>A (p.Glu215Lys)	MMP21	Likely pathogenic	criteria provided, multiple submitters, no conflicts
545548	NM_147191.1(MMP21):c.557G>T (p.Ser186Ile)	MMP21	Likely pathogenic	no assertion criteria provided
976665	NM_147191.1(MMP21):c.281G>C (p.Arg94Pro)	MMP21	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1027776	NM_147191.1(MMP21):c.1123C>T (p.Arg375Cys)	MMP21	Uncertain significance	criteria provided, multiple submitters, no conflicts
1027777	NM_147191.1(MMP21):c.890C>T (p.Thr297Met)	MMP21	Uncertain significance	criteria provided, multiple submitters, no conflicts
2433766	NM_147191.1(MMP21):c.1517T>C (p.Ile506Thr)	MMP21	Uncertain significance	criteria provided, multiple submitters, no conflicts
2507422	NM_147191.1(MMP21):c.626C>G (p.Thr209Arg)	MMP21	Uncertain significance	criteria provided, multiple submitters, no conflicts
2634606	NM_147191.1(MMP21):c.1078C>T (p.Arg360Cys)	MMP21	Uncertain significance	criteria provided, single submitter
2636982	NM_147191.1(MMP21):c.1A>G (p.Met1Val)	MMP21	Uncertain significance	criteria provided, single submitter
3591418	NM_147191.1(MMP21):c.1237+5A>G	MMP21	Uncertain significance	criteria provided, single submitter
4079280	NM_147191.1(MMP21):c.844G>A (p.Val282Ile)	MMP21	Uncertain significance	criteria provided, single submitter
4279807	NM_147191.1(MMP21):c.727G>T (p.Asp243Tyr)	MMP21	Uncertain significance	criteria provided, single submitter
4796701	NM_147191.1(MMP21):c.311T>C (p.Leu104Pro)	MMP21	Uncertain significance	criteria provided, single submitter
4846856	NM_147191.1(MMP21):c.1163G>A (p.Gly388Glu)	MMP21	Uncertain significance	criteria provided, single submitter
2920762	NM_147191.1(MMP21):c.486C>T (p.Tyr162=)	MMP21	Benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 2 · 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
MMP21	Definitive	Autosomal recessive	heterotaxy, visceral, 7, autosomal	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MMP21	Orphanet:101063	Situs inversus totalis
MMP21	Orphanet:157769	Situs ambiguus

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MMP21	HGNC:14357	ENSG00000154485	Q8N119	Matrix metalloproteinase-21	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MMP21	Matrix metalloproteinase-21	Plays a specialized role in the generation of left-right asymmetry during embryogenesis.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Protease	1	36.6×	0.027

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MMP21	Protease	yes		Hemopexin-like_dom, Pept_M10_metallopeptidase, Peptidoglycan-bd-like

Expression context

Cohort genes with no expression data: 0.

Breadth distribution (Bgee present_calls)

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

Top tissues across cohort

Tissue	Cohort genes
corpus epididymis	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
MMP21	160		yes	primordial germ cell in gonad, corpus epididymis, male germ line stem cell (sensu Vertebrata) in testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MMP21	310

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MMP21	Q8N119	84.44

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
determination of heart left/right asymmetry	1	3370.4×	0.002	MMP21
coronary vasculature development	1	624.1×	0.006	MMP21
collagen catabolic process	1	391.9×	0.006	MMP21
determination of left/right symmetry	1	255.3×	0.006	MMP21
hematopoietic progenitor cell differentiation	1	237.3×	0.006	MMP21
extracellular matrix organization	1	122.1×	0.010	MMP21
proteolysis	1	34.2×	0.029	MMP21

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MMP21	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	1	MMP21
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
MMP21	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.