Hereditary sclerosing poikiloderma with tendon and pulmonary involvement

Summary

Hereditary sclerosing poikiloderma with tendon and pulmonary involvement (MONDO:0014310) is a disease caused by FAM111B (GenCC Strong), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: FAM111B (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 21

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		15	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	hereditary sclerosing poikiloderma with tendon and pulmonary involvement
Mondo ID	MONDO:0014310
OMIM	615704
Orphanet	221043
ICD-11	1585528459
UMLS	C3810325
MedGen	816655
GARD	0013218
Is cancer (heuristic)	no

Also known as: hereditary fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis · poikiloderma, hereditary fibrosing, with tendon contractures, myopathy, and pulmonary fibrosis · POIKTMP · POIKTMP syndrome

Data availability: 21 ClinVar variants · 5 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › respiratory system disorder › hereditary sclerosing poikiloderma with tendon and pulmonary involvement

Related subtypes (58): lower respiratory tract disorder, respiratory system cancer, respiratory system benign neoplasm, allergic respiratory disease, paranasal sinus disorder, upper respiratory tract disorder, pertussis, severe acute respiratory syndrome, sleep apnea syndrome, diaphragm disorder, pulmonary tuberculosis, altitude sickness, perinatal asphyxia, pulmonary nodular lymphoid hyperplasia, tracheobronchopathia osteochondroplastica, Williams-Campbell syndrome, cystic fibrosis, growth delay-hydrocephaly-lung hypoplasia syndrome, laryngo-onycho-cutaneous syndrome, congenital pulmonary lymphangiectasia, familial primary pulmonary hypoplasia, Mounier-Kuhn syndrome, Young syndrome, lung agenesis-heart defect-thumb anomalies syndrome, sudden infant death-dysgenesis of the testes syndrome, alpha 1-antitrypsin deficiency, autoimmune interstitial lung disease-arthritis syndrome, mucopolysaccharidosis-plus syndrome, congenital bronchobiliary fistula, bronchogenic cyst, primary ciliary dyskinesia, congenital pulmonary airway malformation, transient hyperammonemia of the newborn, congenital pulmonary sequestration, Siegler-Brewer-Carey syndrome, tracheal agenesis, 16q24.1 microdeletion syndrome, staphylococcal necrotizing pneumonia, pulmonary veno-occlusive disease and/or pulmonary capillary haemangiomatosis, plastic bronchitis, recurrent respiratory papillomatosis, IgG4-related mediastinitis, bronchopulmonary dysplasia, infantile apnea, diffuse alveolar hemorrhage, respiratory or thoracic malformation, pulmonary agenesis, eosinophilic granuloma, disorder of pharynx, respiratory tract neoplasm, pulmonary alveolar proteinosis with hypogammaglobulinemia, respiratory tract infectious disorder, Middle East respiratory syndrome, reactive airway disease, acinar dysplasia, pulmonary hypoplasia, isolated left bronchial isomerism, bronchiectasis and nasal polyposis

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

21 retrieved; paginated sample, class counts are floors:

7 uncertain significance, 6 not provided, 4 likely benign, 3 pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
120218	NM_198947.4(FAM111B):c.1879A>G (p.Arg627Gly)	FAM111B	Pathogenic	no assertion criteria provided
120219	NM_198947.4(FAM111B):c.1883G>A (p.Ser628Asn)	FAM111B	Pathogenic	no assertion criteria provided
1676282	NM_198947.4(FAM111B):c.1886T>G (p.Phe629Cys)	FAM111B	Pathogenic	criteria provided, multiple submitters, no conflicts
120217	NM_198947.4(FAM111B):c.1861T>G (p.Tyr621Asp)	FAM111B	Likely pathogenic	criteria provided, single submitter
1030418	NM_198947.4(FAM111B):c.671C>G (p.Ala224Gly)	FAM111B	Uncertain significance	criteria provided, single submitter
1033669	NM_198947.4(FAM111B):c.368_369insCT (p.Gln124fs)	FAM111B	Uncertain significance	criteria provided, multiple submitters, no conflicts
2664927	NM_198947.4(FAM111B):c.1997C>A (p.Thr666Asn)	FAM111B	Uncertain significance	criteria provided, single submitter
3091672	NM_198947.4(FAM111B):c.296C>T (p.Ala99Val)	FAM111B	Uncertain significance	criteria provided, multiple submitters, no conflicts
3779639	NM_198947.4(FAM111B):c.1018del (p.Gln340fs)	FAM111B	Uncertain significance	criteria provided, single submitter
3891682	NM_198947.4(FAM111B):c.1475T>G (p.Val492Gly)	FAM111B	Uncertain significance	criteria provided, single submitter
4078626	NM_198947.4(FAM111B):c.1394A>G (p.Gln465Arg)	FAM111B	Uncertain significance	criteria provided, single submitter
3248615	NM_198947.4(FAM111B):c.520C>T (p.Arg174Cys)	FAM111B	Likely benign	criteria provided, single submitter
3891680	NM_198947.4(FAM111B):c.1118G>A (p.Arg373Gln)	FAM111B	Likely benign	criteria provided, multiple submitters, no conflicts
4795891	NM_198947.4(FAM111B):c.5del (p.Asn2fs)	FAM111B	Likely benign	criteria provided, single submitter
4820041	NM_198947.4(FAM111B):c.1465C>T (p.Arg489Ter)	FAM111B	Likely benign	criteria provided, single submitter
1192525	NM_198947.4(FAM111B):c.1247T>C (p.Phe416Ser)	FAM111B	not provided	no classification provided
1192526	NM_198947.4(FAM111B):c.1884T>A (p.Ser628Arg)	FAM111B	not provided	no classification provided
1301401	NM_198947.4(FAM111B):c.1881A>T (p.Arg627Ser)	FAM111B	not provided	no classification provided
265953	NM_198947.4(FAM111B):c.1262_1264del (p.Lys421del)	FAM111B	not provided	no classification provided
265954	NM_198947.4(FAM111B):c.1289A>C (p.Gln430Pro)	FAM111B	not provided	no classification provided
265955	NM_198947.4(FAM111B):c.1874C>A (p.Thr625Asn)	FAM111B	not provided	no classification provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · 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
FAM111B	Strong	Autosomal dominant	hereditary sclerosing poikiloderma with tendon and pulmonary involvement	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FAM111B	Orphanet:221043	Hereditary fibrosing poikiloderma-tendon contractures-myopathy-pulmonary fibrosis syndrome

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
FAM111B	HGNC:24200	ENSG00000189057	Q6SJ93	Serine protease FAM111B	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FAM111B	Serine protease FAM111B	Serine protease.

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)
FAM111B	Protease	yes		Peptidase_S1_PA,

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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
buccal mucosa cell	1
ganglionic eminence	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FAM111B	140	ubiquitous	marker	secondary oocyte, buccal mucosa cell, ganglionic eminence

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FAM111B	1,029

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
FAM111B	Q6SJ93	69.32

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
DNA replication	1	165.2×	0.012	FAM111B
proteolysis	1	34.2×	0.029	FAM111B

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
FAM111B	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	FAM111B
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)
FAM111B	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.