Coffin-Siris syndrome 7

Summary

Coffin-Siris syndrome 7 (MONDO:0054831) is a disease caused by DPF2 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: DPF2 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 27

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Coffin-Siris syndrome 7
Mondo ID	MONDO:0054831
OMIM	618027
DOID	DOID:0112369
UMLS	C4747954
MedGen	1648281
GARD	0016287
Is cancer (heuristic)	no

Also known as: CSS7

Data availability: 27 ClinVar variants · 5 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › Coffin-Siris syndrome › Coffin-Siris syndrome 7

Related subtypes (10): Coffin-Siris syndrome 1, intellectual disability, autosomal dominant 14, intellectual disability, autosomal dominant 15, intellectual disability, autosomal dominant 16, intellectual developmental disorder with microcephaly and with or without ocular malformations or hypogonadotropic hypogonadism, Coffin-Siris syndrome 5, Coffin-Siris syndrome 12, Coffin-Siris syndrome 8, Coffin-Siris syndrome 10, Coffin-Siris syndrome 11

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

27 retrieved; paginated sample, class counts are floors:

10 uncertain significance, 7 likely pathogenic, 5 pathogenic, 4 conflicting classifications of pathogenicity, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1173064	NM_006268.5(DPF2):c.1066T>G (p.Cys356Gly)	DPF2	Pathogenic	criteria provided, single submitter
438643	NM_006268.5(DPF2):c.827G>T (p.Cys276Phe)	DPF2	Pathogenic	criteria provided, single submitter
545683	NM_006268.5(DPF2):c.990C>G (p.Cys330Trp)	DPF2	Pathogenic	no assertion criteria provided
545685	NM_006268.5(DPF2):c.1037A>G (p.Asp346Gly)	DPF2	Pathogenic	criteria provided, single submitter
545686	NM_006268.5(DPF2):c.1099+1G>A	DPF2	Pathogenic	no assertion criteria provided
1676450	NM_006268.5(DPF2):c.1099+2dup	DPF2	Likely pathogenic	criteria provided, single submitter
1805984	NM_006268.5(DPF2):c.1067G>C (p.Cys356Ser)	DPF2	Likely pathogenic	criteria provided, single submitter
2442163	NM_006268.5(DPF2):c.1094dup (p.Pro365_Glu366insTer)	DPF2	Likely pathogenic	criteria provided, single submitter
3064790	NM_006268.5(DPF2):c.970T>G (p.Cys324Gly)	DPF2	Likely pathogenic	criteria provided, single submitter
3376275	NM_006268.5(DPF2):c.899G>T (p.Arg300Leu)	DPF2	Likely pathogenic	criteria provided, single submitter
3769178	NM_006268.5(DPF2):c.976G>A (p.Glu326Lys)	DPF2	Likely pathogenic	criteria provided, single submitter
545684	NM_006268.5(DPF2):c.1049G>A (p.Arg350His)	DPF2	Likely pathogenic	criteria provided, single submitter
1028497	NM_006268.5(DPF2):c.904+20C>G	DPF2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1328135	NM_006268.5(DPF2):c.844A>T (p.Ile282Phe)	DPF2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1678611	NM_006268.5(DPF2):c.1169C>A (p.Ser390Tyr)	DPF2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3377195	NM_006268.5(DPF2):c.884G>A (p.Cys295Tyr)	DPF2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1213754	NM_006268.5(DPF2):c.900C>T (p.Arg300=)	DPF2	Uncertain significance	criteria provided, single submitter
1321295	NM_006268.5(DPF2):c.1045G>C (p.Asp349His)	DPF2	Uncertain significance	criteria provided, single submitter
1803136	NM_006268.5(DPF2):c.508G>C (p.Glu170Gln)	DPF2	Uncertain significance	criteria provided, single submitter
2441021	NM_006268.5(DPF2):c.397G>C (p.Ala133Pro)	DPF2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2441022	NM_006268.5(DPF2):c.203C>A (p.Ser68Tyr)	DPF2	Uncertain significance	criteria provided, single submitter
3254756	NM_006268.5(DPF2):c.733C>G (p.Gln245Glu)	DPF2	Uncertain significance	criteria provided, single submitter
3901965	NM_006268.5(DPF2):c.1076del (p.Pro359fs)	DPF2	Uncertain significance	criteria provided, single submitter
3901968	NM_006268.5(DPF2):c.1091C>A (p.Pro364His)	DPF2	Uncertain significance	criteria provided, single submitter
4796516	NM_006268.5(DPF2):c.1045G>T (p.Asp349Tyr)	DPF2	Uncertain significance	criteria provided, single submitter
930733	NM_006268.5(DPF2):c.364C>G (p.Leu122Val)	DPF2	Uncertain significance	criteria provided, single submitter
1639923	NM_006268.5(DPF2):c.302-11C>T	DPF2	Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · 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
DPF2	Strong	Autosomal dominant	Coffin-Siris syndrome 7	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DPF2	Orphanet:1465	Coffin-Siris 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
DPF2	HGNC:9964	ENSG00000133884	Q92785	Zinc finger protein ubi-d4	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DPF2	Zinc finger protein ubi-d4	Plays an active role in transcriptional regulation by binding modified histones H3 and H4.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DPF2	Transcription factor	no		Znf_PHD, Znf_FYVE_PHD, Znf_RING/FYVE/PHD

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
calcaneal tendon	1
oocyte	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DPF2	290	ubiquitous	marker	oocyte, secondary oocyte, calcaneal tendon

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DPF2	1,808

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DPF2	Q92785	9

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. 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
Formation of the canonical BAF (cBAF) complex	1	634.4×	0.004	DPF2
Formation of the embryonic stem cell BAF (esBAF) complex	1	601.0×	0.004	DPF2
Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)	1	456.8×	0.004	DPF2
Regulation of MITF-M-dependent genes involved in pigmentation	1	265.6×	0.005	DPF2
Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs)	1	117.7×	0.008	DPF2

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 myeloid progenitor cell differentiation	1	16852.0×	8e-04	DPF2
regulation of G0 to G1 transition	1	674.1×	0.006	DPF2
regulation of nucleotide-excision repair	1	601.9×	0.006	DPF2
regulation of mitotic metaphase/anaphase transition	1	495.6×	0.006	DPF2
positive regulation of stem cell population maintenance	1	343.9×	0.006	DPF2
positive regulation of double-strand break repair	1	343.9×	0.006	DPF2
regulation of G1/S transition of mitotic cell cycle	1	306.4×	0.006	DPF2
apoptotic signaling pathway	1	224.7×	0.007	DPF2
chromatin remodeling	1	73.0×	0.020	DPF2
nervous system development	1	45.9×	0.028	DPF2
apoptotic process	1	28.7×	0.041	DPF2
negative regulation of transcription by RNA polymerase II	1	17.7×	0.061	DPF2
regulation of transcription by RNA polymerase II	1	11.7×	0.086	DPF2

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
DPF2	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	DPF2

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)
DPF2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.