Helicoid peripapillary chorioretinal degeneration

disease

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Also known as atrophia areataSCRASVEINSSON chorioretinal atrophy

Summary

Helicoid peripapillary chorioretinal degeneration (MONDO:0007176) is a disease caused by TEAD1 (GenCC Strong), with 2 cohort genes.

At a glance

Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
Causal gene: TEAD1 (GenCC Strong)
Cohort genes: 2
ClinVar variants: 7

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		100	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	helicoid peripapillary chorioretinal degeneration
Mondo ID	MONDO:0007176
MeSH	C566236
OMIM	108985
Orphanet	86813
DOID	DOID:0111228
ICD-11	896652469
SNOMED CT	724384008
UMLS	C1862382
MedGen	354733
GARD	0016757
Is cancer (heuristic)	no

Also known as: atrophia areata · SCRA · SVEINSSON chorioretinal atrophy · Sveinsson chorioretinal atrophy

Data availability: 7 ClinVar variants · 5 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › retinal disorder › retinal degeneration › inherited retinal dystrophy › helicoid peripapillary chorioretinal degeneration

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

7 retrieved; paginated sample, class counts are floors:

2 benign, 2 pathogenic, 1 uncertain significance, 1 benign/likely benign, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
813239	NM_022367.4(SEMA4A):c.985C>T (p.Gln329Ter)	SEMA4A	Pathogenic	criteria provided, single submitter
12630	NM_021961.6(TEAD1):c.1261T>C (p.Tyr421His)	TEAD1	Pathogenic	no assertion criteria provided
984436	NM_021961.6(TEAD1):c.1261T>A (p.Tyr421Asn)	TEAD1	Conflicting classifications of pathogenicity	no assertion criteria provided
3175565	NM_021961.6(TEAD1):c.932A>G (p.Gln311Arg)	TEAD1	Uncertain significance	criteria provided, single submitter
1166402	NM_021961.6(TEAD1):c.513C>T (p.Asp171=)	TEAD1	Benign	criteria provided, multiple submitters, no conflicts
522308	NM_021961.6(TEAD1):c.675C>T (p.Leu225=)	TEAD1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
802657	NM_021961.6(TEAD1):c.331-907AT[4]	TEAD1	Benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 4 · 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
TEAD1	Strong	Autosomal dominant	helicoid peripapillary chorioretinal degeneration	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TEAD1	Orphanet:86813	Helicoid peripapillary chorioretinal degeneration
SEMA4A	Orphanet:1872	Cone rod dystrophy
SEMA4A	Orphanet:440437	Familial colorectal cancer Type X
SEMA4A	Orphanet:791	Retinitis pigmentosa

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TEAD1	HGNC:11714	ENSG00000187079	P28347	Transcriptional enhancer factor TEF-1	gencc,clinvar
SEMA4A	HGNC:10729	ENSG00000196189	Q9H3S1	Semaphorin-4A	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TEAD1	Transcriptional enhancer factor TEF-1	Transcription factor which plays a key role in the Hippo signaling pathway, a pathway involved in organ size control and tumor suppression by restricting proliferation and promoting apoptosis.
SEMA4A	Semaphorin-4A	Cell surface receptor for PLXNB1, PLXNB2, PLXNB3 and PLXND1 that plays an important role in cell-cell signaling.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 1 · 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	8.6×	0.225
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TEAD1	Other/Unknown	no		TEA/ATTS_dom, TEF_metazoa, TEA/ATTS_sf
SEMA4A	Scaffold/PPI	no		Semap_dom, Plexin_repeat, WD40/YVTN_repeat-like_dom_sf

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
biceps brachii	1
skeletal muscle tissue of biceps brachii	1
skeletal muscle tissue of rectus abdominis	1
leukocyte	1
monocyte	1
mononuclear cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TEAD1	263	ubiquitous	marker	skeletal muscle tissue of rectus abdominis, biceps brachii, skeletal muscle tissue of biceps brachii
SEMA4A	219	broad	marker	monocyte, mononuclear cell, leukocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TEAD1	2,544
SEMA4A	997

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TEAD1	P28347	14

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SEMA4A	Q9H3S1	85.05

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 13. Enrichment computed across 2 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
Nervous system development	2	42.9×	0.007	TEAD1, SEMA4A
RUNX3 regulates YAP1-mediated transcription	1	713.8×	0.009	TEAD1
YAP1- and WWTR1 (TAZ)-stimulated gene expression	1	380.7×	0.010	TEAD1
Other semaphorin interactions	1	300.5×	0.010	SEMA4A
Semaphorin interactions	1	196.9×	0.010	SEMA4A
EGR2 and SOX10-mediated initiation of Schwann cell myelination	1	184.2×	0.010	TEAD1
Developmental Biology	2	14.5×	0.010	TEAD1, SEMA4A
Transcriptional regulation by RUNX3	1	135.9×	0.012	TEAD1
Regulation of PD-L1(CD274) transcription	1	54.4×	0.026	TEAD1
Axon guidance	1	22.6×	0.057	SEMA4A
RNA Polymerase II Transcription	1	11.3×	0.103	TEAD1
Gene expression (Transcription)	1	8.9×	0.118	TEAD1
Generic Transcription Pathway	1	7.5×	0.128	TEAD1

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of excitatory synapse assembly	1	2808.7×	0.004	SEMA4A
positive regulation of inhibitory synapse assembly	1	2808.7×	0.004	SEMA4A
regulation of endothelial cell migration	1	1053.2×	0.006	SEMA4A
T-helper 1 cell differentiation	1	766.0×	0.007	SEMA4A
hippo signaling	1	366.4×	0.010	TEAD1
negative chemotaxis	1	324.1×	0.010	SEMA4A
embryonic organ development	1	240.7×	0.012	TEAD1
semaphorin-plexin signaling pathway	1	200.6×	0.012	SEMA4A
neural crest cell migration	1	168.5×	0.013	SEMA4A
positive regulation of miRNA transcription	1	145.3×	0.014	TEAD1
positive regulation of cell growth	1	91.6×	0.020	TEAD1
negative regulation of angiogenesis	1	84.3×	0.020	SEMA4A
regulation of cell shape	1	61.5×	0.025	SEMA4A
protein-containing complex assembly	1	56.9×	0.025	TEAD1
axon guidance	1	45.3×	0.029	SEMA4A
angiogenesis	1	31.2×	0.038	SEMA4A
positive regulation of cell migration	1	30.9×	0.038	SEMA4A
positive regulation of DNA-templated transcription	1	14.0×	0.078	TEAD1
positive regulation of transcription by RNA polymerase II	1	7.4×	0.137	TEAD1
regulation of transcription by RNA polymerase II	1	5.8×	0.164	TEAD1

Therapeutics

Drug target analysis

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

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
TEAD1	1	2
SEMA4A	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PIRLINDOLE	2	TEAD1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
TEAD1	85	Binding:82, Functional:3

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

1 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)
PIRLINDOLE	2	TEAD1

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	1	TEAD1
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	SEMA4A

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)
SEMA4A	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: TEAD1, SEMA4A