First-degree atrioventricular block

Summary

First-degree atrioventricular block (MONDO:0000466) is a disease with 1 cohort gene and 3 clinical trials.

At a glance

• Cohort genes: 1
• ClinVar variants: 2
• Clinical trials: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	first-degree atrioventricular block
Mondo ID	MONDO:0000466
DOID	DOID:0050821
ICD-10-CM	I44.0
ICD-11	1438248929
NCIT	C62015
SNOMED CT	270492004
UMLS	C0085614
MedGen	43215
Is cancer (heuristic)	no

Also known as: atrioventricular block first degree · atrioventricular block, first degree · AV block first degree · first degree atrioventricular block · first degree AV block

Data availability: 2 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › heart disorder › heart conduction disease › atrioventricular block › first-degree atrioventricular block

Related subtypes (3): second-degree atrioventricular block, third-degree atrioventricular block, congenital heart block

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:

2 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
4530630	NM_170741.4(KCNJ16):c.439G>A (p.Val147Met)	KCNJ16	Uncertain significance	criteria provided, single submitter
222729	NM_000257.4(MYH7):c.4717G>A (p.Glu1573Lys)	LOC126861897	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

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

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
KCNJ16	HGNC:6262	ENSG00000153822	Q9NPI9	Inward rectifier potassium channel 16	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KCNJ16	Inward rectifier potassium channel 16	Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it.

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
Ion channel	1	111.5×	0.009

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
KCNJ16	Ion channel	yes		K_chnl_inward-rec_Kir5, K_chnl_inward-rec_Kir_cyto, Ig_E-set

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
caput epididymis	1
nephron tubule	1
renal medulla	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KCNJ16	212	broad	marker	renal medulla, nephron tubule, caput epididymis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KCNJ16	894

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KCNJ16	Q9NPI9	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 12. 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
Potassium transport channels	1	3806.7×	0.003	KCNJ16
G protein gated Potassium channels	1	1142.0×	0.004	KCNJ16
Inwardly rectifying K+ channels	1	713.8×	0.004	KCNJ16
Activation of GABAB receptors	1	601.0×	0.004	KCNJ16
GABA B receptor activation	1	543.8×	0.004	KCNJ16
Activation of G protein gated Potassium channels	1	393.8×	0.004	KCNJ16
Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits	1	393.8×	0.004	KCNJ16
GABA receptor activation	1	317.2×	0.005	KCNJ16
Potassium Channels	1	134.3×	0.010	KCNJ16
Neurotransmitter receptors and postsynaptic signal transmission	1	100.2×	0.012	KCNJ16
Transmission across Chemical Synapses	1	76.1×	0.014	KCNJ16
Neuronal System	1	44.3×	0.023	KCNJ16

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
regulation of monoatomic ion transmembrane transport	1	732.7×	0.005	KCNJ16
potassium ion import across plasma membrane	1	366.4×	0.005	KCNJ16
potassium ion transport	1	191.5×	0.007	KCNJ16
potassium ion transmembrane transport	1	135.9×	0.007	KCNJ16

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
KCNJ16	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	1	KCNJ16
D	Druggable family + AlphaFold only, no drug	0
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)
KCNJ16	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 3.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	3

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01275833	Not specified	TERMINATED	Restoration of Atrioventricular Synchrony Trial
NCT01985802	Not specified	COMPLETED	Pacing in First-degree AV-block
NCT02150538	Not specified	UNKNOWN	BiventRicular Pacing in prolongEd Atrio-Ventricular intervaL: the REAL-CRT Study