Dyskeratosis congenita, autosomal recessive 7

Summary

Dyskeratosis congenita, autosomal recessive 7 (MONDO:0800370) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	dyskeratosis congenita, autosomal recessive 7
Mondo ID	MONDO:0800370
UMLS	C4225283
MedGen	903803
GARD	0026529
Is cancer (heuristic)	no

Also known as: DKCB7

Data availability: 2 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › hereditary neoplastic syndrome › dyskeratosis congenita › dyskeratosis congenita, autosomal recessive 7

Related subtypes (15): dyskeratosis congenita, autosomal dominant 1, dyskeratosis congenita, autosomal recessive 1, Revesz syndrome, dyskeratosis congenita, autosomal recessive 2, dyskeratosis congenita, autosomal recessive 3, dyskeratosis congenita, autosomal dominant 2, dyskeratosis congenita, autosomal dominant 3, dyskeratosis congenita, autosomal recessive 6, dyskeratosis congenita, autosomal dominant 6, autosomal recessive dyskeratosis congenita 4, dyskeratosis congenita, digenic, DKC1-related disorder, dyskeratosis congenita, autosomal dominant 4, dyskeratosis congenita and related telomere biology disorder, dyskeratosis congenita, autosomal recessive 8

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

2 retrieved; paginated sample, class counts are floors:

1 pathogenic, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
208983	NM_001082486.2(ACD):c.250_252del (p.Lys84del)	ACD	Pathogenic	criteria provided, single submitter
208984	NM_001082486.2(ACD):c.1213C>A (p.Pro405Thr)	ACD	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ACD	Orphanet:3322	Hoyeraal-Hreidarsson syndrome
ACD	Orphanet:397692	Hereditary isolated aplastic anemia
ACD	Orphanet:618	Familial melanoma

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
ACD	HGNC:25070	ENSG00000102977	Q96AP0	Adrenocortical dysplasia protein homolog	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ACD	Adrenocortical dysplasia protein homolog	Component of the shelterin complex (telosome) that is involved in the regulation of telomere length and protection.

Protein-family classification

Druggable: 0 · Difficult: 0 · 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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ACD	Other/Unknown	no		TPP1/Est3, ACD

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
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ACD	282	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ACD	1,044

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ACD	Q96AP0	19

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 28. Enrichment computed across 1 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
Depurination	1	1631.4×	0.005	ACD
Depyrimidination	1	951.7×	0.005	ACD
Base-Excision Repair, AP Site Formation	1	878.5×	0.005	ACD
Telomere C-strand synthesis initiation	1	815.7×	0.005	ACD
Processive synthesis on the C-strand of the telomere	1	761.3×	0.005	ACD
Telomere C-strand (Lagging Strand) Synthesis	1	761.3×	0.005	ACD
Base Excision Repair	1	713.8×	0.005	ACD
Removal of the Flap Intermediate from the C-strand	1	634.4×	0.005	ACD
Extension of Telomeres	1	601.0×	0.005	ACD
Telomere Extension By Telomerase	1	456.8×	0.006	ACD
Polymerase switching on the C-strand of the telomere	1	423.0×	0.006	ACD
Telomere Maintenance	1	368.4×	0.006	ACD
Meiosis	1	285.5×	0.008	ACD
Packaging Of Telomere Ends	1	219.6×	0.008	ACD
Chromosome Maintenance	1	211.5×	0.008	ACD
Recognition and association of DNA glycosylase with site containing an affected purine	1	203.9×	0.008	ACD
Cleavage of the damaged purine	1	203.9×	0.008	ACD
Reproduction	1	190.3×	0.008	ACD
Recognition and association of DNA glycosylase with site containing an affected pyrimidine	1	184.2×	0.008	ACD
Cleavage of the damaged pyrimidine	1	184.2×	0.008	ACD
Inhibition of DNA recombination at telomere	1	167.9×	0.008	ACD
DNA Damage/Telomere Stress Induced Senescence	1	163.1×	0.008	ACD
Meiotic synapsis	1	141.0×	0.008	ACD
Cellular Senescence	1	137.6×	0.008	ACD
DNA Repair	1	98.5×	0.011	ACD
Cellular responses to stress	1	36.8×	0.029	ACD
Cell Cycle	1	36.0×	0.029	ACD
Cellular responses to stimuli	1	31.5×	0.032	ACD

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
segmentation	1	8426.0×	0.001	ACD
regulation of establishment of protein localization to telomere	1	5617.3×	0.001	ACD
telomere assembly	1	4213.0×	0.001	ACD
protection from non-homologous end joining at telomere	1	2407.4×	0.001	ACD
establishment of protein localization to telomere	1	2106.5×	0.001	ACD
protein localization to chromosome, telomeric region	1	1532.0×	0.002	ACD
telomere capping	1	1296.3×	0.002	ACD
urogenital system development	1	991.3×	0.002	ACD
telomere maintenance via telomerase	1	732.7×	0.002	ACD
negative regulation of telomere maintenance via telomerase	1	732.7×	0.002	ACD
positive regulation of telomere maintenance	1	510.7×	0.003	ACD
embryonic limb morphogenesis	1	401.2×	0.003	ACD
telomere maintenance	1	267.5×	0.004	ACD
skeletal system development	1	125.8×	0.009	ACD
intracellular protein transport	1	64.8×	0.015	ACD

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
ACD	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	1	ACD

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)
ACD	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.